CN116323666A - Fgfr3抗体和使用方法 - Google Patents
Fgfr3抗体和使用方法 Download PDFInfo
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- CN116323666A CN116323666A CN202180051281.1A CN202180051281A CN116323666A CN 116323666 A CN116323666 A CN 116323666A CN 202180051281 A CN202180051281 A CN 202180051281A CN 116323666 A CN116323666 A CN 116323666A
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Abstract
提供了抗FGFR3抗原结合蛋白及其抗原结合结合片段。还提供了抑制FGFR3活性的方法和治疗FGFR3介导的疾病和障碍的方法。
Description
相关申请的交叉引用
本申请要求2020年8月21提交的美国临时申请号63/068,575的优先权权益，将所述临时申请的内容出于所有目的通过引用以其整体并入。
技术领域
本公开文本涉及抗成纤维细胞生长因子受体3(抗FGFR3)抗原结合蛋白或其抗原结合片段(诸如抗体及其片段)的组合物及其使用方法。
背景技术
成纤维细胞生长因子受体3(FGFR3)是部分地参与骨骼发育的负调节、在生长板软骨细胞中高度表达的蛋白质(Sarabipour等人Biochim Biophys Acta.1858(7Pt A):1436-1442.2016)。FGFR3是具有3个Ig样结构域(D1-D3)的单程膜受体酪氨酸激酶。FGFR3与FGFR3配体(诸如FGF18)的结合触发配体依赖性受体二聚化，这导致酪氨酸激酶激活和下游信号转导。这种信号传导级联尤其调节软骨细胞增殖和分化。
FGFR3是成纤维细胞生长因子受体家族的成员，所述家族还包括FGFR1、FGFR2和FGFR4。受体家族的每个成员都是单通道膜受体酪氨酸激酶，并且共享3个Ig样结构域的特征。此外，受体家族的每个成员都与其他成员具有高度的同源性。出于这个原因，开发FGFR3特异性抑制剂的策略已被证明具有挑战性。尽管如此，重要的是开发FGFR3特异性抑制剂，其不与其他成纤维细胞生长因子受体家族成员发生交叉反应以避免在治疗FGFR3介导的疾病或障碍中发生不需要的副作用。
因此，本领域需要鉴定出实现对FGFR3活性的有效抑制的抗原结合蛋白或其抗原结合片段。此类抗原结合蛋白或其抗原结合片段可以用于治疗FGFR3介导的疾病和障碍。
发明内容
本文公开了抗FGFR3抗原结合蛋白或其抗原结合片段，诸如抗体及其抗原结合片段。本公开文本的抗原结合蛋白或其抗原结合片段诸如抗FGFR3抗体及其抗原结合片段适用于治疗FGFR3介导的疾病和障碍。
在一个方面，本公开文本提供了一种与成纤维细胞生长因子受体3(FGFR3)特异性结合的抗原结合蛋白或其抗原结合片段，其包含抗体重链可变(VH)结构域和抗体轻链可变(VL)结构域，其中：(a)所述VH结构域包含：含有氨基酸序列GX1TFTDX2E(SEQ ID NO:157)的CDR-H1序列，其中X1包括Y或D或由其组成并且X2包括F或Y或由其组成；含有氨基酸序列IDPETGX3T(SEQ ID NO:158)的CDR-H2序列，其中X3包括G或S或由其组成；或含有氨基酸序列INPNNGX4T(SEQ ID NO:159)的CDR-H2序列，其中X4包括G或V或由其组成；或含有氨基酸序列VX5PETGGT(SEQ ID NO:160)的CDR-H2序列，其中X5包括D或E或由其组成；含有氨基酸序列TRX6YX7GYX8X9X10X11DY(SEQ ID NO:161)的CDR-H3序列，其中X6包括T或N或由其组成，X7包括D或E，X8包括S或P或由其组成，X9包括Q、R或Y或由其组成，X10包括T或A或由其组成，X11包括F或M或由其组成；以及所述VL结构域包含：含有氨基酸序列QS X12LYS X13N X14KNY(SEQ IDNO:162)的CDR-L1序列，其中X12包括L或V或由其组成，X13包括N、D或S或由其组成，并且X14包括Q或N或由其组成；含有氨基酸序列X15AS(SEQ ID NO:163)的CDR-L2序列，其中X15包括W、Y或F或由其组成；含有氨基酸序列QQYYSYRT(SEQ ID NO:75)、LQYDNLLWT(SEQ ID NO:81)或HQYLSX16YT(SEQ ID NO:290)的CDR-L3序列，其中X16包括P或S或由其组成；(b)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGAMDY(SEQ ID NO:78)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；(c)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGSMDF(SEQ ID NO:84)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；(d)所述VH结构域包含：含有氨基酸序列GYTVTDYY(SEQ ID NO:88)的CDR-H1序列；含有氨基酸序列INPNNGVT(SEQ ID NO:89)的CDR-H2序列；含有氨基酸序列AREEDFDGFDY(SEQ ID NO:90)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QDVSTG(SEQ ID NO:91)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列QQHYSTPLT(SEQ ID NO:93)的CDR-L3序列；(e)所述VH结构域包含：含有氨基酸序列GSTFSDFE(SEQ ID NO:94)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；含有氨基酸序列TRNYDGYSQTX17DY(SEQ ID NO:308)的CDR-H3序列，其中X17包括M或F；以及所述VL结构域包含：含有氨基酸序列QSVLYSX18NQKNY(SEQ ID NO:309)的CDR-L1序列，其中X18包括S或D；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列；或(f)所述VH结构域包含：含有氨基酸序列GSTFTDFE(SEQ ID NO:100)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；含有氨基酸序列TRNYDGYSQTX17DY(SEQ ID NO:308)的CDR-H3序列，其中X17包括M或F；以及所述VL结构域包含：含有氨基酸序列QSVLYSX18NQKNY(SEQ ID NO:309)的CDR-L1序列，其中X18包括S或D；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ IDNO:70)、GDTFTDYE(SEQ ID NO:295)或GYTFTDFE(SEQ ID NO:296)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)、VDPETGGT(SEQ ID NO:297)、IDPETGST(SEQ IDNO:298)或VEPETGGT(SEQ ID NO:299)的CDR-H2序列；含有氨基酸序列TRTYDGYPYAMDY(SEQID NO:72)、TRTYEGYPYAMDY(SEQ ID NO:300)或TRTYDGYPYAFDY(SEQ ID NO:301)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QSLLYSNNQKNY(SEQ ID NO:73)、QSVLYSNNNKNY(SEQ ID NO:302)或QSVLYSDNQKNY(SEQ ID NO:306)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)、YAS(SEQ ID NO:303)或FAS(SEQ ID NO:304)的CDR-L2序列；含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列；(b)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGAMDY(SEQ ID NO:78)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；(c)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGSMDF(SEQ ID NO:84)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；(d)所述VH结构域包含：含有氨基酸序列GYTVTDYY(SEQ ID NO:88)的CDR-H1序列；含有氨基酸序列INPNNGVT(SEQ ID NO:89)的CDR-H2序列；含有氨基酸序列AREEDFDGFDY(SEQ ID NO:90)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QDVSTG(SEQ ID NO:91)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列QQHYSTPLT(SEQ ID NO:93)的CDR-L3序列；(e)所述VH结构域包含：含有氨基酸序列GSTFSDFE(SEQ ID NO:94)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；含有氨基酸序列TRNYDGYSQTMDY(SEQ ID NO:96)或TRNYDGYSQTFDY(SEQ ID NO:305)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QSVLYSSNQKNY(SEQ ID NO:97和103)或QSVLYSDNQKNY(SEQ ID NO:306)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列；或(f)所述VH结构域包含：含有氨基酸序列GSTFTDFE(SEQ ID NO:100)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；含有氨基酸序列TRNYDGYSRTMDY(SEQ ID NO:102)或TRNYDGYSRTFDY(SEQ IDNO:307)的CDR-H3序列；以及所述VL结构域包含：含有氨基酸序列QSVLYSSNQKNY(SEQ IDNO:97和103)或QSVLYSDNQKNY(SEQ ID NO:306)的CDR-L1序列；含有氨基酸序列WAS(SEQ IDNO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列。
在某些实施方案中，(a)所述VH结构域包含选自以下的氨基酸序列：SEQ ID NO:6、SEQ ID NO:18、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQ ID NO:10、SEQ IDNO:110、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQ ID NO:119、SEQ ID NO:120、SEQ ID NO:121、SEQ ID NO:122、SEQ ID NO:57和SEQ ID NO:58；以及所述VL结构域包含选自以下的氨基酸序列：SEQ ID NO:7、SEQ ID NO:19、SEQ ID NO:112、SEQID NO:113、SEQ ID NO:114、SEQ ID NO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ ID NO:131、SEQID NO:132、SEQ ID NO:60和SEQ ID NO:61；(b)所述VH结构域包含氨基酸序列SEQ ID NO:8，并且所述VL结构域包含氨基酸序列SEQ ID NO:9；(c)所述VH结构域包含氨基酸序列SEQID NO:10，并且所述VL结构域包含氨基酸序列SEQ ID NO:11；(d)所述VH结构域包含氨基酸序列SEQ ID NO:12，并且所述VL结构域包含氨基酸序列SEQ ID NO:13；(e)所述VH结构域包含选自以下的氨基酸序列：SEQ ID NO:14、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22和SEQ ID NO:23；以及所述VL结构域包含选自以下的氨基酸序列：SEQ ID NO:15、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26和SEQ ID NO:27；(f)所述VH结构域包含选自以下的氨基酸序列：SEQ ID NO:16、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30和SEQ ID NO:31；所述VL结构域包含选自以下的氨基酸序列：SEQ ID NO:17、SEQ ID NO:32、SEQ ID NO:33、SEQID NO:34和SEQ ID NO:35。
在某些实施方案中，所述抗体重链包含氨基酸序列SEQ ID NO:63或65，并且所述抗体轻链包含氨基酸序列SEQ ID NO:67或69。
在某些实施方案中，所述VH结构域与氨基酸序列SEQ ID NO:6、SEQ ID NO:8、SEQID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQID NO:31、SEQ ID NO:56、SEQ ID NO:57、SEQ ID NO:58、SEQ ID NO:63、SEQ ID NO:65、SEQID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQ ID NO:109、SEQ ID NO:110、SEQ ID NO:111、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQ ID NO:119、SEQID NO:120、SEQ ID NO:121或SEQ ID NO:122具有至少约90％同一性或至少约95％同一性，并且其中所述VL结构域与氨基酸序列SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ IDNO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:24、SEQ ID NO:25、SEQ IDNO:26、SEQ ID NO:27、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ IDNO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:67、SEQ ID NO:69、SEQ ID NO:112、SEQID NO:113、SEQ ID NO:114、SEQ ID NO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ ID NO:131或SEQ ID NO:132具有至少约90％同一性或至少约95％同一性。
在某些实施方案中，所述抗原结合蛋白或其片段包含与氨基酸序列SEQ ID NO:63或65具有至少约90％同一性或至少约95％同一性的抗体重链和与氨基酸序列SEQ ID NO:67或69具有至少约90％同一性或至少约95％同一性的抗体轻链。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ IDNO:70)的CDR-H1序列、含有氨基酸序列IDPETGGT(SEQ ID NO:71)的CDR-H2序列、和含有氨基酸序列TRTYDGYPYAMDY(SEQ ID NO:72)的CDR-H3序列；以及(b)所述VL结构域包含：含有氨基酸序列QSLLYSNNQKNY(SEQ ID NO:73)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:74)的CDR-L2序列、和含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列。在其一些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:6，并且所述VL结构域包含氨基酸序列SEQ ID NO:7。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ IDNO:76)的CDR-H1序列、含有氨基酸序列INPNNGGT(SEQ ID NO:77)的CDR-H2序列、和含有氨基酸序列ARERDYDGAMDY(SEQ ID NO:78)的CDR-H3序列；以及(b)所述VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79)的CDR-L1序列、含有氨基酸序列YTS(SEQ ID NO:80)的CDR-L2序列、和含有氨基酸序列LQYDNLLWT(SEQ ID NO:81)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:8，并且所述VL结构域包含氨基酸序列SEQ ID NO:9。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ IDNO:82)的CDR-H1序列、含有氨基酸序列INPNNGGT(SEQ ID NO:83)的CDR-H2序列、和含有氨基酸序列ARERDYDGSMDF(SEQ ID NO:84)的CDR-H3序列；以及(b)所述VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:85)的CDR-L1序列、含有氨基酸序列YTS(SEQ ID NO:86)的CDR-L2序列、和含有氨基酸序列LQYDNLLWT(SEQ ID NO:87)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:10，并且所述VL结构域包含氨基酸序列SEQ ID NO:11。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GYTVTDYY(SEQ IDNO:88)的CDR-H1序列、含有氨基酸序列INPNNGVT(SEQ ID NO:89)的CDR-H2序列、和含有氨基酸序列AREEDFDGFDY(SEQ ID NO:90)的CDR-H3序列；以及(b)所述VL结构域包含：含有氨基酸序列QDVSTG(SEQ ID NO:91)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:92)的CDR-L2序列、和含有氨基酸序列QQHYSTPLT(SEQ ID NO:93)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:12，并且所述VL结构域包含氨基酸序列SEQ ID NO:13。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GSTFSDFE(SEQ IDNO:94)的CDR-H1序列、含有氨基酸序列IDPETGGT(SEQ ID NO:95)的CDR-H2序列、和含有氨基酸序列TRNYDGYSQTMDY(SEQ ID NO:96)的CDR-H3序列；以及(b)所述VL结构域包含：含有氨基酸序列QSVLYSSNQKNY(SEQ ID NO:97)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:98)的CDR-L2序列、和含有氨基酸序列HQYLSSYT(SEQ ID NO:99)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:14，并且所述VL结构域包含氨基酸序列SEQ ID NO:15。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GSTFTDFE(SEQ IDNO:100)的CDR-H1序列、含有氨基酸序列IDPETGGT(SEQ ID NO:101)的CDR-H2序列、和含有氨基酸序列TRNYDGYSRTMDY(SEQ ID NO:102)的CDR-H3序列；以及(b)所述VL结构域包含：含有氨基酸序列QSVLYSSNQKNY(SEQ ID NO:103)的CDR-L1序列、含有氨基酸序列WAS(SEQ IDNO:104)的CDR-L2序列、和含有氨基酸序列HQYLSSYT(SEQ ID NO:105)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:16，并且所述VL结构域包含氨基酸序列SEQ ID NO:17。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ IDNO:70)的CDR-H1序列、含有氨基酸序列VDPETGGT(SEQ ID NO:297)的CDR-H2序列、和含有氨基酸序列TRTYDGYPYAFDY(SEQ ID NO:301)的CDR-H3序列；以及(b)所述VL结构域包含：含有氨基酸序列QSVLYSNNNKNY(SEQ ID NO:302)的CDR-L1序列、含有氨基酸序列WAS(SEQ IDNO:74、92、98、104)的CDR-L2序列、和含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:57，并且所述VL结构域包含氨基酸序列SEQ ID NO:19或59。
在某些实施方案中，所述抗体重链包含氨基酸序列SEQ ID NO:63，并且所述抗体轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ IDNO:70)的CDR-H1序列、含有氨基酸序列VDPETGGT(SEQ ID NO:297)的CDR-H2序列、和含有氨基酸序列TRTYDGYPYAFDY(SEQ ID NO:301)的CDR-H3序列；以及(b)所述VL结构域包含：含有氨基酸序列QSVLYSDNQKNY(SEQ ID NO:306)的CDR-L1序列、含有氨基酸序列FAS(SEQ IDNO:304)的CDR-L2序列、和含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:57，并且所述VL结构域包含氨基酸序列SEQ ID NO:61。
在某些实施方案中，所述抗体重链包含氨基酸序列SEQ ID NO:65，并且所述抗体轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段结合包含氨基酸序列SEQ ID NO:133的人FGFR3多肽。
在某些实施方案中，所述抗原结合蛋白或其抗原结合片段结合包含氨基酸序列SEQ ID NO:134的人FGFR3多肽。
在某些实施方案中，所述抗原结合蛋白或其抗原结合片段结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至L163。
在某些实施方案中，所述抗原结合蛋白或其抗原结合片段结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至N170。
在某些实施方案中，所述抗原结合蛋白或其抗原结合片段结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至D160和G197至L213。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段是嵌合或人源化抗体或其抗原结合结合片段。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段是人抗体或其抗原结合结合片段。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段是单克隆抗体或其抗原结合结合片段。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段包含一个或多个包含Fc区的全长抗体重链。
在某些实施方案中，所述Fc区是人IgG1 Fc区。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段包括抗体F(ab)、F(ab')2、Fab'-SH、Fv或scFv片段。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段包括抗体F(ab)片段。
在某些实施方案中，所述抗体F(ab)片段包含SEQ ID NO:56、和SEQ ID NO:54的前约100个氨基酸。
在某些实施方案中，所述抗体F(ab)片段包含SEQ ID NO:57、和SEQ ID NO:54的前约100个氨基酸。
在某些实施方案中，所述抗体F(ab)片段包含SEQ ID NO:58、和SEQ ID NO:54的前约100个氨基酸。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:141，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:142。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:143，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:144。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:145，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:146。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:147，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:148。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:149，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:150。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:151，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:152。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段包括与小鼠和食蟹猴FGFR3的交叉反应性。
在某些实施方案中，所述抗原结合或其抗原结合结合片段蛋白不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段不与FGFR1、FGFR2和FGFR4中的每一种结合。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以100μM或更大的亲和力与FGFR1、FGFR2和FGFR4中的每一种结合。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以10nM或更小的平衡解离常数(KD)结合人FGFR3。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以10-4或更大的解离速率(Kd)结合人FGFR3。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以5μg/ml或更小的IC50抑制配体诱导的FGFR3二聚化。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以5μg/ml或更小的IC50抑制FGFR3受体激活和下游信号传导。
在某些实施方案中，所述抗原结合蛋白或其抗原结合片段抑制FGFR3G380R突变体的活性。
在某些实施方案中，所述抗原结合蛋白或其抗原结合片段能够穿透骨生长板。
在某些实施方案中，所述抗原结合蛋白或其抗原结合片段能够降低在骨生长板中FGFR3与其配体的结合。
在另一个方面，本公开文本提供了一种药物组合物，其包含以上列举的抗原结合蛋白或其抗原结合片段和药学上可接受的载体。
在另一个方面，本公开文本提供了一种分离的核酸分子，其编码以上列举的抗原结合蛋白或其抗原结合片段。
在另一个方面，本公开文本提供了一种表达载体，其包含以上列举的核酸分子。
在另一个方面，本公开文本提供了一种宿主细胞，其包含以上列举的表达载体。
在另一个方面，本公开文本提供了一种用于治疗受试者的FGFR3介导的疾病或障碍的方法，其包括向有需要的受试者施用以上列举的抗原结合蛋白或其抗原结合片段。
在某些实施方案中，所述FGFR3介导的疾病或障碍是软骨发育不全。
在某些实施方案中，所述软骨发育不全是FGFR3G380R+软骨发育不全。
在某些实施方案中，患有软骨发育不全的受试者包括选自以下的一种或多种症状：近端肢体缩短、短指、大头伴有显著前额额部隆起、面中部小伴有鼻梁扁平、脊柱后凸、脊柱前凸、内翻、外翻、耳部感染、睡眠呼吸暂停、和脑积水。
在某些实施方案中，所述FGFR3介导的疾病或障碍是癌症。
在某些实施方案中，所述癌症是膀胱癌黑色素瘤、尿路上皮癌和子宫内膜癌。
在一个方面，本公开文本提供了一种用于治疗受试者的软骨发育不全的方法，其包括向有需要的受试者施用与FGFR3特异性结合的抗原结合蛋白片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
在一个方面，本公开文本提供了一种用于抑制受试者的骨生长板中FGFR3活性和表达中的一者或两者的方法，其包括向受试者施用与FGFR3特异性结合的抗原结合蛋白片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
在一个方面，本公开文本提供了一种与成纤维细胞生长因子受体3(FGFR3)特异性结合的抗原结合蛋白或其抗原结合片段，其包含抗体重链可变(VH)结构域和抗体轻链可变(VL)结构域，其中所述抗原结合蛋白结合包含氨基酸序列SEQ ID NO:134的人FGFR3多肽。
在某些实施方案中，所述抗原结合蛋白结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至L163。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至N170。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至D160和G197至L213。
在一个方面，本公开文本提供了一种具有与成纤维细胞生长因子受体3(FGFR3)表位的结合特异性的抗原结合蛋白或其抗原结合片段，其包含抗体重链可变(VH)结构域和抗体轻链可变(VL)结构域，其中所述抗原结合蛋白或其抗原结合片段与包含选自以下的VH/VL结构域氨基酸序列对的抗体竞争结合至FGFR3：SEQ ID NO:6/SEQ ID NO:7、SEQ ID NO:8/SEQ ID NO:9、SEQ ID NO:10/SEQ ID NO:11、SEQ ID NO:12/SEQ ID NO:13、SEQ ID NO:14/SEQ ID NO:15和SEQ ID NO:16/SEQ ID NO:17。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段是嵌合或人源化抗体或其抗原结合结合片段。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段是人抗体或其抗原结合结合片段。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段是单克隆抗体或其抗原结合结合片段。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段包含一个或多个包含Fc区的全长抗体重链。
在某些实施方案中，所述Fc区是人IgG1 Fc区。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段包括抗体F(ab)、F(ab')2、Fab'-SH、Fv或scFv片段。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段包括抗体F(ab)片段。
在某些实施方案中，所述抗体F(ab)片段包含SEQ ID NO:56、和SEQ ID NO:54的前约100个氨基酸。
在某些实施方案中，所述抗体F(ab)片段包含重链，所述重链包含SEQ ID NO:57、和SEQ ID NO:54的前约100个氨基酸。
在某些实施方案中，所述抗体F(ab)片段包含重链，所述重链包含SEQ ID NO:58、和SEQ ID NO:54的前约100个氨基酸。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:141、164、173、182、191、200、209、218、227、236、245、254、263、272或281，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:142。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:143、165、174、183、192、201、210、219、228、237、246、255、264、273或282，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:144。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:145、166、175、184、193、202、211、220、229、238、247、256、265、274或283，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:146。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:147、167、176、185、194、203、212、221、230、239、248、257、266、275或284，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:148。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:149、168、177、186、195、204、213、222、231、240、249、258、267、276或285，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:150。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:151、169、178、187、196、205、214、223、232、241、250、259、268、277或286，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:152。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段包括具有与小鼠和食蟹猴FGFR3的交叉反应性。
在某些实施方案中，所述抗原结合或其抗原结合结合片段蛋白不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段不与FGFR1、FGFR2和FGFR4中的每一种结合。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以100μM或更大的亲和力平衡解离常数(KD)与FGFR1、FGFR2和FGFR4中的每一种结合。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以10nM或更小的平衡解离常数(KD)结合人FGFR3。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以10-4或更大的解离速率(Kd)结合人FGFR3。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以5μg/ml或更小的IC50抑制配体诱导的FGFR3二聚化。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段以5μg/ml或更小的IC50抑制FGFR3受体激活和下游信号传导。
在某些实施方案中，所述抗原结合蛋白或其抗原结合片段抑制FGFR3G380R突变体的活性。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段能够穿透骨生长板。
在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段能够降低在骨生长板中FGFR3与其配体的结合。在某些实施方案中，所述抗原结合蛋白或其抗原结合结合片段能够降低在骨生长板中FGFR3的激酶活性。
还提供了一种药物组合物，其包含如本文所述的抗原结合蛋白或其抗原结合片段。在某些实施方案中，所述药物组合物包含药学上可接受的载体。
还提供了一种分离的核酸分子，其编码如本文所述的抗原结合蛋白或其抗原结合片段。还提供了一种表达盒，其包含所述核酸分子。还提供了一种表达载体，其包含所述分离的核酸分子。进一步提供了一种宿主细胞，其包含所述表达载体、所述表达盒或所述核酸分子。
进一步提供了一种用于治疗受试者的FGFR3介导的疾病或障碍的方法。在某些实施方案中，所述方法包括向有需要的受试者施用如本文所述的抗原结合蛋白或其抗原结合片段。在某些实施方案中，所述FGFR3介导的疾病或障碍是软骨发育不全。在某些实施方案中，所述软骨发育不全是FGFR3G380R+软骨发育不全。
在某些实施方案中，所述FGFR3介导的疾病或障碍是癌症。
在某些实施方案中，所述癌症是膀胱癌黑色素瘤、尿路上皮癌和子宫内膜癌。
还提供了一种用于治疗受试者的软骨发育不全的方法。在某些实施方案中，所述方法包括向有需要的受试者施用与FGFR3特异性结合的抗原结合蛋白片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
还提供了一种用于抑制受试者的骨生长板中FGFR3活性和表达中的一者或两者的方法。在某些实施方案中，所述方法包括向受试者施用与FGFR3特异性结合的抗原结合蛋白片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
在某些实施方案中，所述受试者是儿童。在某些实施方案中，所述儿童是婴儿。在某些实施方案中，所述婴儿是新生儿。
还提供了一种用于预防或减轻受试者的软骨发育不全的一种或多种症状的方法。在某些实施方案中，所述方法包括向受试者施用与FGFR3特异性结合的抗原结合蛋白或其抗原结合蛋白片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
附图说明
根据以下说明性实施方案的详细描述结合附图，将更充分地理解本公开文本的前述和其他特征和优点。所述专利或申请文件含有至少一张彩色附图。在请求并支付必要的费用后，官方将会提供带有一个或多个彩色附图的本专利或专利申请公开案的副本。
图1示意性地描绘了成纤维细胞生长因子受体3(FGFR3)同种型IIIc。
图2描绘了用氢氘交换(HDX)质谱法生成的热图，所述氢氘交换质谱法用于通过测量FGFR3上的酰胺氢氘交换来确定FGFR3上针对所选抗体的表位。
图3描绘了来自内化测定的荧光图像，以检测抗FGFR3抗体在KMS-11细胞中的内化。
图4图形化地描绘了相对于抗体总量，抗FGFR3抗体内化的平均量。
图5A-图5C图形化地描绘了抗FGFR3抗体KC18(图5A)、KE58(图5B)、KE94(图5C)对FGFR3二聚化的抑制。通过在共表达β-半乳糖苷酶-prolink(PK)和FGFR3(FGFR3-PK)融合蛋白以及-半乳糖苷酶-酶受体(EA)和FGFR3(FGFR3-EA)融合蛋白的U2OS细胞中的化学发光测定来评价抑制。
图6描绘了抗FGFR3抗体KC18、KE63和KE94的比对。
图7描绘了抗FGFR3抗体KC18_Hu18与变体的比对。Hu18残基的突变以绿色或红色突出显示。
图8A-图8C描绘的图展示了人源化抗FGFR3抗体Hu18(图8A)、Hu44(图8B)和Hu46(图8C)对Erk磷酸化的抑制的IC50值。对Erk磷酸化的抑制通过同质时间分辨荧光(HTRF)测定来测定。
图9A-图9B图形化地描绘了抗FGFR3抗体KC18(图9A)、KE63(图9B)和KE94(图9B)及其对应的Fab片段的相对Erk磷酸化抑制。
图10A-图10C图形化地描绘了呈不同形式的抗FGFR3抗体KC18的相对Erk磷酸化抑制。图10A描绘了呈全长抗体(KC18)、Fab片段(Kc18 Fab)、单臂单价抗体(MetMab)、和聚乙二醇化Fab片段(PEG)的KC18在WT细胞中的抑制作用。图10B描绘了呈全长抗体(IgG)、Fab片段、单臂单价抗体(MetMab)和聚乙二醇化Fab片段(PEG)的KC18在Ach细胞中的抑制作用。图10C描绘了KC18 Fab片段与半衰期延长部分(使用人白蛋白)的纳米抗体缀合物(KC18 Fab-HLE)，其具有和没有人血清白蛋白(HSA)或小鼠血清白蛋白(MSA)。Erk磷酸化在HTRF测定中测量并且与同种型对照(Iso)进行比较。
图11图形化地描绘了人源化抗FGFR3抗体Hu18、Hu44和Hu46对Erk磷酸化的抑制。使用HTRF测定确定对Erk磷酸化的抑制。
图12A-图12B图形化地描绘了软骨发育不全小鼠模型(Ach)中的股骨(图12A)和胫骨(图12B)长度，所述小鼠模型是转基因小鼠，其在胶原II启动子下过表达具有G380R突变的小鼠FGFR3蛋白。从3日龄到20日龄，向小鼠皮下施用KC18 Fab片段。
图13A-图13B图形化地描绘了Ach小鼠模型的椎骨(图13A)和颅骨(图13B)长度。对于颅骨测量，NL＝鼻长；FL＝额骨长度；并且PL＝顶骨长度。
图14图形化地描绘了经盐水或KC18 Fab片段处理的WT和Ach小鼠模型的脑体积。
图15A图形化地描绘了经盐水或KC18 Fab片段处理的WT和Ach小鼠模型的脊柱后凸指数。图15B描绘了使用小鼠模型计算脊柱后凸指数。
图16A图形化地描绘了经媒介物或KC18 Fab片段处理的Ach小鼠模型的股骨生长板(GP)体积。图16B描绘了经媒介物或KC18 Fab片段处理的Ach小鼠模型的股骨直径。
图17图形化地描绘了与经媒介物处理的那些相比，Ach小鼠模型的胫骨的次级骨化中心增加。
具体实施方式
提供了抗原结合蛋白或其抗原结合片段。还提供了抑制一种或多种FGFR3活性的方法和治疗FGFR3介导的疾病和障碍的方法。
通常，本文所述的结合细胞和组织培养、分子生物学、免疫学、微生物学、遗传学以及蛋白质和核酸化学和杂交使用的命名法是本领域中熟知并且一般使用的那些。除非另外指示，否则本文所提供的方法和技术通常是根据本领域熟知并且如本说明书通篇引用和讨论的各个通用和更具体参考文献中所述的常规方法来进行的。酶促反应和纯化技术是根据制造商的说明进行的，如本领域通常所实现或如本文所述的。与本文所述的分析化学、合成有机化学以及医学化学和药物化学结合使用的命名法及其实验室程序和技术是本领域中熟知并且一般使用的那些。使用标准技术来进行化学合成、化学分析、药物制备、配制和递送以及患者的治疗。
除非本文另外定义，否则本文所用的科学和技术术语具有本领域普通技术人员通常理解的含义。在任何潜在歧义的情况下，本文所提供的定义优先于任何字典或非固有定义。除非上下文另外要求，否则单数术语应包括复数，并且复数术语应包括单数。除非另外说明，否则“或”的使用意指“和/或”。术语“包括(including)”以及其他形式如“包括”(“includes”和“included”)的使用不是限制性的。
为了可以更容易理解本公开文本，首先定义某些术语。
成纤维细胞生长因子受体3(FGFR3)
如本文所用，术语“FGFR3”或“成纤维细胞生长因子受体3”或“CD333”是指由FGFR3基因编码的FGFR3蛋白。FGFR3属于成纤维细胞生长因子受体家族，所述家族还包括FGFR1、FGFR2和FGFR4。与其他成纤维细胞生长因子受体家族成员一样，FGFR3是具有3个Ig样结构域(D1、D2和D3)的单程膜受体酪氨酸激酶。配体依赖性受体二聚化导致酪氨酸激酶激活和下游信号转导。FGFR3经受可变剪接，导致多种同种型，包括同种型IIIb和同种型IIIc。IIIb和IIIc由外显子8和9的可变剪接产生。IIIb和IIIc具有相同的Ig1(D1)和Ig2(D2)结构域，但Ig3(D3)结构域不同。FGFR3 IIIc是软骨细胞中的主要FGFR3同种型，并且介导FGFR3配体FGF18在关节软骨中的合成代谢作用。FGFR3的结构和功能进一步详细地描述在Olsen等人(PNAS.101(4):935-940.2004)中，将所述文献出于所有目的通过引用以其整体并入本文。
下面列举了人FGFR3同种型IIIc氨基酸序列。
MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLV
FGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNA
SHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDT
GAPYWTRPERMDKKLLAVPAANTVRFRCPAAGNPTPSISWLKNGREFRG
EHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLE
RSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGS
KVGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSI
GFSHHSAWLVVLPAEEELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLC
RLRSPPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEG
PTLANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDR
AAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACT
QGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVS
CAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHN
LDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGG
SPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTF
KQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPPAPPSSGGSRT(SEQID NO:135)
FGFR3中的突变可能导致某些不希望的病症。FGFR3的跨膜结构域中的G380R突变与所有软骨发育不全病例中的98％相关。具有G380R突变的FGFR3可以称为FGFR3G380R，并且下面列举了人FGFR3G380R同种型IIIc的序列。
MGAPACALALCVAVAIVAGASSESLGTEQRVVGRAAEVPGPEPGQQEQLV
FGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNA
SHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDT
GAPYWTRPERMDKKLLAVPAANTVRFRCPAAGNPTPSISWLKNGREFRG
EHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLE
RSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGS
KVGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSI
GFSHHSAWLVVLPAEEELVEADEAGSVYAGILSYRVGFFLFILVVAAVTLC
RLRSPPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEG
PTLANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDR
AAKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACT
QGGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVS
CAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHN
LDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGG
SPYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTF
KQLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPPAPPSSGGSRT(SEQID NO:133)
抗原结合蛋白
如本文所用，术语“抗体”或“抗原结合蛋白”是指与抗原或表位(例如，FGFR3抗原或表位)特异性结合或免疫反应的免疫球蛋白分子，并且包括多克隆和单克隆抗体两者以及功能性抗体片段，包括但不限于片段抗原结合(Fab)片段、F(ab')2片段、Fab'片段、Fv片段、重组IgG(rIgG)片段、单链可变片段(scFv)和单结构域抗体(例如，sdAb、sdFv、纳米抗体)片段。术语“抗体”包括免疫球蛋白的基因工程化或以其他方式修饰的形式，诸如细胞内抗体、肽抗体、嵌合抗体、完全人抗体、人源化抗体、中间位使能性抗体、异源缀合抗体(例如，双特异性抗体、双体抗体、三抗体、四抗体、串联二scFv、串联三scFv)等。除非另外说明，否则术语“抗体”应当理解为涵盖其功能性抗体片段。如本文所用，术语“功能性抗体片段”是指与衍生片段的目的抗体具有至少80％、至少85％、至少90％或至少95％亲和力的抗体片段。
如本文所用，术语“互补决定区”或“CDR”是指在抗体可变区内的赋予抗原特异性和结合亲和力的氨基酸序列。通常，在每个重链可变区中有三个CDR(CDR-H1、CDR-H2、CDR-H3)，并且在每个轻链可变区中有三个CDR(CDR-L1、CDR-L2、CDR-L3)。“框架区”或“FR”在本领域中已知是指重链和轻链的可变区的非CDR部分。通常，在每个重链可变区中有四个FR(FR-H1、FR-H2、FR-H3和FR-H4)，并且在每个轻链可变区中有四个FR(FR-L1、FR-L2、FR-L3和FR-L4)。
给定CDR或FR的精确氨基酸序列边界可以使用许多熟知的方案中的任一种容易地确定，包括以下文献中所述的那些：Kabat等人(1991),“Sequences of Proteins ofImmunological Interest,”第5版Public Health Service,National Institutes ofHealth,贝塞斯达,马里兰州(“Kabat”编号方案)；Al-Lazikani等人,(1997)JMB 273,927-948(“Chothia”编号方案)；MacCallum等人,J.Mol.Biol.262:732-745(1996),“Antibody-antigen interactions:Contact analysis and binding site topography,”J.Mol.Biol.262,732-745。(“Contact”编号方案)，Lefranc M P等人,“IMGT uniquenumbering for immunoglobulin and T cell receptor variable domains and Igsuperfamily V-like domains,”Dev Comp Immunol,2003年1月；27(1):55-77(“IMGT”编号方案)，以及Honegger A和Pluckthun A,“Yet another numbering scheme forimmunoglobulin variable domains:an automatic modeling and analysis tool,”JMol Biol,2001年6月8日；309(3):657-70,(AHo编号方案)。
给定CDR或FR的边界可能根据用于鉴定的方案而变化。例如，Kabat方案是基于结构比对，而Chothia方案是基于结构信息。Kabat和Chothia方案的编号都是基于最常见的抗体区序列长度，其中通过插入字母(例如，“30a”)提供插入，并且在一些抗体中出现缺失。这两种方案将某些插入和缺失(“插入缺失(indel)”)放置在不同的位置，从而产生不同的编号。Contact方案是基于对复杂晶体结构的分析，并且在许多方面与Chothia编号方案相似。
给定抗体或其区域(诸如其可变区)的“CDR”或“互补决定区”或单独指定的CDR(例如，CDR-H1、CDR-H2、CDR-H3)应理解为涵盖如由任何已知方案所定义的一个(或特定)互补决定区。同样，“FR”或“框架区”或单独指定的FR(例如，“FR-H1”、“FR-H2”)涵盖如由任何已知方案所定义的一个(或特定的)框架区。在一些情况下，指定了用于鉴定特定CDR或FR的方案，诸如，如通过IMGT、Kabat、Chothia、AbM或Conta ct方法定义的CDR。在其他情况下，给出了CDR或FR的特定氨基酸序列。除非另有指定，否则本公开文本中提及的所有特定CDR氨基酸序列均是IMGT CDR。然而，由其他方案定义的替代CDR也包括在本公开文本中，诸如由abYsis关键注释(Website:abysis.org/abysis/sequence_input/key_annotation/key_annotation.cgi)确定的那些。
如本文所用，术语“特异性结合(specifically binds)”、“特异性结合(specifically binding)”、“结合特异性”或“特异性识别”是指对抗原(例如，FGFR3抗原)展现出明显的亲和力并且不与非FGFR3蛋白靶标展现出显著的交叉反应性的抗原结合蛋白或其抗原结合片段。如本文所用，术语“亲和力”是指抗原结合蛋白或其抗原结合片段抗原结合位点与其结合的表位之间相互作用的强度。如本领域技术人员容易理解的，抗原结合蛋白亲和力可以报告为以摩尔浓度(M)计的解离常数(KD)。本公开文本的抗原结合蛋白或其抗原结合片段具有在约10-6M至约10-12M(即，低微摩尔至皮摩尔范围)、约10-7M至10-11M、约10-8M至约10-10M、约10-9M范围内的KD值。在某些实施方案中，抗原结合蛋白或其抗原结合片段具有约10-6M、10-7M、10-8M、10-9M、10-10M、10-11M、或10-12M的结合亲和力。在某些实施方案中，抗原结合蛋白或其抗原结合片段具有约10-7M至约10-9M(纳摩尔范围)的结合亲和力。
特异性结合可以根据用于确定此类结合的任何本领域公认的手段来确定。在一些实施方案中，特异性结合是通过竞争性结合测定(例如，ELISA)或Biacore测定确定的。在某些实施方案中，在约20℃、25℃、30℃或37℃下进行测定。
抗FGFR3抗原结合蛋白
在一个方面，本公开文本提供了抗原结合蛋白及其抗原结合片段，其具有与FGFR3的结合特异性。
示例性抗FGFR3抗原结合蛋白及其抗原结合片段CDR列举在下表1和表4中。示例性抗FGFR3抗原结合蛋白及其抗原结合片段可变重(VH)和可变轻(VL)结构域列举在下表3、表8、表9和表13中。示例性抗FGFR3抗原结合蛋白全长重链和轻链列举在下表14中。
表1.抗体重链和轻链CDR区
在某些实施方案中，抗FGFR3抗原结合蛋白及其抗原结合片段包含抗体重链可变(VH)结构域，其包含CDR-H1序列、CDR-H2序列和CDR-H3序列。CDR-H1序列包含氨基酸序列GX1TFTDX2E(SEQ ID NO:157)，其中X1包括Y或D并且X2包括F或Y；CDR-H2序列包含氨基酸序列IDPETGX3T(SEQ ID NO:158)，其中X3包括G或S；或CDR-H2序列包含氨基酸序列INPNNGX4T(SEQ ID NO:159)，其中X4包括G或V；或CDR-H2序列包含氨基酸序列VX5PETGGT(SEQ ID NO:160)，其中X5包括D或E；并且CDR-H3序列包含氨基酸序列TRX6YX7GYX8X9X10X11DY(SEQ ID NO:161)，其中X6包括T或N，X7包括D或E，X8包括S或P，X9包括Q、R或Y，X10包括T或A，X11包括F或M。
在某些实施方案中，抗FGFR3抗原结合蛋白及其抗原结合片段包括抗体轻链可变(VL)结构域，其包含CDR-L1序列、CDR-L2序列和CDR-L3序列。CDR-L1序列包含氨基酸序列QSX12LYS X13N X14KNY(SEQ ID NO:162)，其中X12包括L或V，X13包括N、D或S，并且X14包括Q或N；CDR-L2序列包含氨基酸序列X15AS(SEQ ID NO:163)，其中X15包括W、Y或F；以及CDR-L3序列包含氨基酸序列QQYYSYRT(SEQ ID NO:75)、LQYDNLLWT(SEQ ID NO:81)或HQYLSX16YT(SEQID NO:290)，其中X16包括P或S。
在一个方面，本公开文本提供了一种与成纤维细胞生长因子受体3(FGFR3)特异性结合的抗原结合蛋白或其片段，其包含抗体重链可变(VH)结构域和抗体轻链可变(VL)结构域，其中：
(a)VH结构域包含：含有氨基酸序列GX1TFTDX2E(SEQ ID NO:157)的CDR-H1序列，其中X1包括Y或D并且X2包括F或Y；含有氨基酸序列IDPETGX3T(SEQ ID NO:158)的CDR-H2序列，其中X3包括G或S；或含有氨基酸序列INPNNGX4T(SEQ ID NO:159)的CDR-H2序列，其中X4包括G或V；或含有氨基酸序列VX5PETGGT(SEQ ID NO:160)的CDR-H2序列，其中X5包括D或E；含有氨基酸序列TRX6YX7GYX8X9X10X11DY(SEQ ID NO:161)的CDR-H3序列，其中X6包括T或N，X7包括D或E，X8包括S或P，X9包括Q、R或Y，X10包括T或A，X11包括F或M；并且VL结构域包含：含有氨基酸序列QS X12LYS X13N X14KNY(SEQ ID NO:162)的CDR-L1序列，其中X12包括L或V，X13包括N、D或S，并且X14包括Q或N；含有氨基酸序列X15AS(SEQ ID NO:163)的CDR-L2序列，其中X15包括W、Y或F；含有氨基酸序列QQYYSYRT(SEQ ID NO:75)、LQYDNLLWT(SEQ ID NO:81)或HQYLSX16YT(SEQ ID NO:290)的CDR-L3序列，其中X16包括P或S；
(b)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGAMDY(SEQ ID NO:78)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；
(c)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGSMDF(SEQ ID NO:84)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；
(d)所述VH结构域包含：含有氨基酸序列GYTVTDYY(SEQ ID NO:88)的CDR-H1序列；含有氨基酸序列INPNNGVT(SEQ ID NO:89)的CDR-H2序列；含有氨基酸序列AREEDFDGFDY(SEQ ID NO:90)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QDVSTG(SEQ ID NO:91)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列QQHYSTPLT(SEQ ID NO:93)的CDR-L3序列；
(e)所述VH结构域包含：含有氨基酸序列GSTFSDFE(SEQ ID NO:94)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；含有氨基酸序列TRNYDGYSQTX17DY(SEQ ID NO:308)的CDR-H3序列，其中X17包括M或F；并且VL结构域包含：含有氨基酸序列QSVLYSX18NQKNY(SEQ ID NO:309)的CDR-L1序列，其中X18包括S或D；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ IDNO:99和105)的CDR-L3序列；或
(f)所述VH结构域包含：含有氨基酸序列GSTFTDFE(SEQ ID NO:100)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；含有氨基酸序列TRNYDGYSQTX17DY(SEQ ID NO:308)的CDR-H3序列，其中X17包括M或F；并且VL结构域包含：含有氨基酸序列QSVLYSX18NQKNY(SEQ ID NO:309)的CDR-L1序列，其中X18包括S或D；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ IDNO:99和105)的CDR-L3序列。
在某些实施方案中，抗原结合蛋白或其片段包含VH结构域和VL结构域，其中：
(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ ID NO:70)、GDTFTDYE(SEQID NO:295)或GYTFTDFE(SEQ ID NO:296)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ IDNO:71、95和101)、VDPETGGT(SEQ ID NO:297)、IDPETGST(SEQ ID NO:298)或VEPETGGT(SEQID NO:299)的CDR-H2序列；含有氨基酸序列TRTYDGYPYAMDY(SEQ ID NO:72)、TRTYEGYPYAMDY(SEQ ID NO:300)或TRTYDGYPYAFDY(SEQ ID NO:301)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QSLLYSNNQKNY(SEQ ID NO:73)、QSVLYSNNNKNY(SEQ ID NO:302)或QSVLYSDNQKNY(SEQ ID NO:306)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)、YAS(SEQ ID NO:303)或FAS(SEQ ID NO:304)的CDR-L2序列；含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列；
(b)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGAMDY(SEQ ID NO:78)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；
(c)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGSMDF(SEQ ID NO:84)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；
(d)所述VH结构域包含：含有氨基酸序列GYTVTDYY(SEQ ID NO:88)的CDR-H1序列；含有氨基酸序列INPNNGVT(SEQ ID NO:89)的CDR-H2序列；含有氨基酸序列AREEDFDGFDY(SEQ ID NO:90)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QDVSTG(SEQ ID NO:91)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98、104)的CDR-L2序列；含有氨基酸序列QQHYSTPLT(SEQ ID NO:93)的CDR-L3序列；
(e)所述VH结构域包含：含有氨基酸序列GSTFSDFE(SEQ ID NO:94)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；含有氨基酸序列TRNYDGYSQTMDY(SEQ ID NO:96)或TRNYDGYSQTFDY(SEQ ID NO:305)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QSVLYSSNQKNY(SEQ ID NO:97和103)或QSVLYSDNQKNY(SEQ IDNO:306)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列or HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列；或
(f)所述VH结构域包含：含有氨基酸序列GSTFTDFE(SEQ IDNO:100)的CDR-H1序列；含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；含有氨基酸序列TRNYDGYSRTMDY(SEQ ID NO:102)或TRNYDGYSRTFDY(SEQ ID NO:307)的CDR-H3序列；并且VL结构域包含：含有氨基酸序列QSVLYSSNQKNY(SEQ ID NO:97和103)或QSVLYSDNQKNY(SEQ IDNO:306)的CDR-L1序列；含有氨基酸序列WAS(SEQ ID NO:74、92、98、104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列。
在某些实施方案中，FGFR3抗原结合蛋白及其抗原结合片段包含表3、8、9或13中列举的一个VH结构域和一个VL结构域。在某些实施方案中，提供了示例性抗原结合蛋白或其抗原结合片段：
表1.1示例性抗原结合蛋白或抗原结合片段的重链和轻链
在某些实施方案中，抗FGFR3抗原结合蛋白或其片段包含上表1.1的一对重链和轻链。
在某些实施方案中，抗FGFR3抗原结合蛋白或其片段包含VH结构域和VL结构域，其中：
(a)所述VH结构域包含选自以下的氨基酸序列：SEQ ID NO:6、SEQ ID NO:18、SEQID NO:57、SEQ ID NO:58、SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQ ID NO:109、SEQ ID NO:110、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQID NO:119、SEQ ID NO:120、SEQ ID NO:121和SEQ ID NO:122；并且VL结构域包含选自以下的氨基酸序列：SEQ ID NO:7、SEQ ID NO:19、SEQ ID NO:60、SEQ ID NO:61SEQ ID NO:112、SEQ ID NO:113、SEQ ID NO:114、SEQ ID NO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ IDNO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ ID NO:131和SEQ ID NO:132；
(b)所述VH结构域包含氨基酸序列SEQ ID NO:8，并且所述VL结构域包含氨基酸序列SEQ ID NO:9；
(c)所述VH结构域包含氨基酸序列SEQ ID NO:10，并且所述VL结构域包含氨基酸序列SEQ ID NO:11；
(d)所述VH结构域包含氨基酸序列SEQ ID NO:12，并且所述VL结构域包含氨基酸序列SEQ ID NO:13；
(e)所述VH结构域包含选自以下的氨基酸序列：SEQ ID NO:14、SEQ ID NO:20、SEQID NO:21、SEQ ID NO:22和SEQ ID NO:23；并且VL结构域包含选自以下的氨基酸序列：SEQID NO:15、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26和SEQ ID NO:27；
(f)所述VH结构域包含选自以下的氨基酸序列：SEQ ID NO:16、SEQ ID NO:28、SEQID NO:29、SEQ ID NO:30和SEQ ID NO:31；VL结构域包含选自以下的氨基酸序列：SEQ IDNO:17、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34和SEQ ID NO:35。
在某些实施方案中，所述抗体重链包含氨基酸序列SEQ ID NO:63或65，并且所述抗体轻链包含氨基酸序列SEQ ID NO:67或69。
还提供了如本文所述的抗FGFR3抗原结合蛋白或其片段的变体。在某些实施方案中，变体的VH结构域与氨基酸序列SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQ ID NO:12、SEQ ID NO:14、SEQ ID NO:16、SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:21、SEQ IDNO:22、SEQ ID NO:23、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ IDNO:57、SEQ ID NO:58,SEQ ID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQ ID NO:109、SEQ ID NO:110、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQ ID NO:118、SEQ IDNO:119、SEQ ID NO:120、SEQ ID NO:121或SEQ ID NO:122具有至少约80％、至少至少约81％、至少约82％、至少约83％、至少约84％、至少约85％、至少约86％、至少约87％、至少约88％、至少约89％、至少约90％同一性、至少约91％同一性、至少约92％同一性、至少约93％同一性、至少约94％同一性、至少约95％同一性、至少约96％同一性、至少约97％同一性、至少约98％同一性或至少约99％同一性，并且变体的VL结构域与氨基酸序列SEQ ID NO:7、SEQ ID NO:9、SEQ ID NO:11、SEQ ID NO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:112、SEQ IDNO:113、SEQ ID NO:114、SEQ ID NO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ ID NO:131或SEQ IDNO:132具有至少约80％、至少至少约81％、至少约82％、至少约83％、至少约84％、至少约85％、至少约86％、至少约87％、至少约88％、至少约89％、至少约90％同一性、至少约91％同一性、至少约92％同一性、至少约93％同一性、至少约94％同一性、至少约95％同一性、至少约96％同一性、至少约97％同一性、至少约98％同一性或至少约99％同一性。用于获得同一性的氨基酸序列比对可以是任何常规氨基酸序列比对工具，并且序列比对算法包括Needle-Wunsch算法、Smith-Waterman算法或Karling&Altschul算法，但不限于此；氨基酸序列比对工具包括BLAST(基本局部比对搜索工具(Basic Local Alignment SearchTool))、BLAT(BLAST样比对工具(BLAST-like Alignment Tool))、Grapped BLAST或FASTA，但不限于此。在某些实施方案中，变体具有如本文所述的抗FGFR3抗原结合蛋白或其片段的所有相同重链CDR和轻链CDR，并且重链和/或轻链上的恒定区中具有修饰。
在某些实施方案中，抗FGFR3抗原结合蛋白或其片段包含与氨基酸序列SEQ IDNO:63或65具有至少约80％、至少至少约81％、至少约82％、至少约83％、至少约84％、至少约85％、至少约86％、至少约87％、至少约88％、至少约89％、至少约90％同一性、至少约91％同一性、至少约92％同一性、至少约93％同一性、至少约94％同一性、至少约95％同一性、至少约96％同一性、至少约97％同一性、至少约98％同一性或至少约99％同一性的抗体重链；和与氨基酸序列SEQ ID NO:67或69具有至少约80％、至少至少约81％、至少约82％、至少约83％、至少约84％、至少约85％、至少约86％、至少约87％、至少约88％、至少约89％、至少约90％同一性、至少约91％同一性、至少约92％同一性、至少约93％同一性、至少约94％同一性、至少约95％同一性、至少约96％同一性、至少约97％同一性、至少约98％同一性,或至少约99％同一性的抗体轻链。
在某些实施方案中，抗FGFR3抗原结合蛋白或其片段包含VH结构域和VL结构域，其中：(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ ID NO:70)的CDR-H1序列、含有氨基酸序列VDPETGGT(SEQ ID NO:297)的CDR-H2序列、和含有氨基酸序列TRTYDGYPYAFDY(SEQ ID NO:301)的CDR-H3序列；以及(b)VL结构域包含：含有氨基酸序列QSVLYSNNNKNY(SEQ ID NO:302)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列、和含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:57，并且所述VL结构域包含氨基酸序列SEQ ID NO:19或59。
在某些实施方案中，所述抗体重链包含氨基酸序列SEQ ID NO:63，并且所述抗体轻链包含氨基酸序列SEQ ID NO:67。在某些实施方案中，所述抗体重链包含氨基酸序列SEQID NO:65，并且所述抗体轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，抗FGFR3抗原结合蛋白或其片段包含VH结构域和VL结构域，其中：(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ ID NO:70)的CDR-H1序列、含有氨基酸序列VDPETGGT(SEQ ID NO:297)的CDR-H2序列、和含有氨基酸序列TRTYDGYPYAFDY(SEQ ID NO:301)的CDR-H3序列；以及(b)VL结构域包含：含有氨基酸序列QSVLYSDNQKNY(SEQ ID NO:306)的CDR-L1序列、含有氨基酸序列FAS(SEQ ID NO:304)的CDR-L2序列、和含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列。
在某些实施方案中，所述VH结构域包含氨基酸序列SEQ ID NO:57，并且所述VL结构域包含氨基酸序列SEQ ID NO:61。
在某些实施方案中，所述抗体重链包含氨基酸序列SEQ ID NO:65，并且所述抗体轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白及其抗原结合片段包含与由表9中的核酸序列编码的表1、表3、表4、表8、表13或表14或蛋白质序列中的任何序列具有至少约80％、至少约80％、至少约85％、至少约90％、至少约95％、至少约96％、至少约97％、至少约98％、至少约99％或100％序列同一性的一个或多个序列。
本文还提供了用于抗FGFR3抗原结合蛋白及其抗原结合片段的人框架区。下面提供了人框架区的非限制性例子。
表1.2抗FGFR3抗原结合蛋白及其抗原结合片段的人框架区
在一些实施方案中，抗FGFR3抗原结合蛋白和抗原结合片段包含与FGFR3结合的三个重链CDR，诸如小鼠抗体KC18、KE35、KE42、KE58、KE63或KE94的三个重链CDR，和人重链可变区框架。在某些实施方案中，抗FGFR3抗原结合蛋白和抗原结合片段进一步包含与FGFR3结合的三个轻链CDR，诸如小鼠抗体KC18、KE35、KE42、KE58、KE63或KE94的三个轻链CDR，和人轻链可变区框架。在某些实施方案中，人重链可变区框架包含SEQ ID NO:318至328中的任一个。在某些实施方案中，人轻链可变区框架包含SEQ ID NO:329至339中的任一个。在某些实施方案中，人重链可变区框架包含与SEQ ID NO:318至328中的任一个具有至少80％、至少81％、至少82％、至少83％、至少84％、至少85％、至少86％、至少87％、至少88％、至少89％、至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％或更大同一性的序列。在某些实施方案中，人轻链可变区框架包含与SEQ ID NO:329至339中的任一个具有至少80％、至少81％、至少82％、至少83％、至少84％、至少85％、至少86％、至少87％、至少88％、至少89％、至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％或更大同一性的序列。在某些实施方案中，此类抗FGFR3抗原结合蛋白和抗原结合片段以约100nM或更小、约90nM或更小、约80nM或更小、约70nM或更小、约60nM或更小、约50nM或更小、约40nM或更小、约30nM或更小、约20nM或更小、约10nM或更小、约9nM或更小、约8nM或更小、约7nM或更小、约6nM或更小、约5nM或更小、约4nM或更小、约3nM或更小、约2.89nM或更小、约2nM或更小、约1.5或更小、约1.4或更小、约1.23或更小、约1.2或更小、或约1nM或更小、约0.8或更小或约0.6或更小的平衡解离常数(KD)结合人FGFR3。其中的“XnM或更小”包括“小于X nM”的实施方案。其中的“更小”可以意指例如至约2.8nM、至约1.3nM、至约1.1nM、至约0.7nM或至约0.5nM。这些下限可以用于与任何前述上限形成范围，诸如约3nM或<3nM至约2.8nM、约1.5nM或<1.5nM至约1.3nM、约1.3nM或<1.3nM至约1.1nM、约0.9nM或<0.9nM至约0.7nM、或约0.7nM或<0.7nM至约0.5nM。其中的“约X”可以意指例如“X±5％”、“X±4％”、“X±4％”、“X±3％”、“X±2％”、“X±1％”或“X±0.5％”。在某些实施方案中，nM值是如通过表面等离子共振测定诸如Biacore测定获得的。
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白及其抗原结合片段是嵌合抗体或人源化抗体。在某些实施方案中，抗原结合蛋白是人源化抗体。
在某些实施方案中，抗原结合蛋白是单克隆抗体。
在某些实施方案中，抗原结合蛋白包含一个或多个包含Fc区的全长抗体重链。在某些实施方案中，所述Fc区是人IgG1 Fc区。在某些实施方案中，所述Fc区是人IgG4 Fc区。
在某些实施方案中，抗体Fc区包含一个或多个降低Fc效应子功能的突变。在某些实施方案中，所述一个或多个突变降低抗体依赖性细胞毒性(ADCC)、抗体依赖性细胞吞噬作用(ADCP)或补体依赖性细胞毒性(CDC)中的一种或多种。在某些实施方案中，人IgG1 Fc区包含L234A和L235A突变。在某些实施方案中，人IgG4 Fc区包含F234A和L235A突变。这些IgG1和IgG4突变也分别称为“LALA”和“FALA”突变，并且进一步详细描述在Xu等人(CellImmunol.2000；200:16-26)中。在某些实施方案中，人IgG4 Fc区包含一个或多个稳定化突变，包括但不限于降低或阻止二硫键形成和体内fab臂交换(FAE)的IgG4铰链中的突变。在某些实施方案中，人IgG4 Fc区包含S228P突变。IgG4铰链突变更详细地描述在Angal等人(Mol.Immunol.1993；30:105-108)。在某些实施方案中，人IgG4 Fc区包含S228P突变和L235A突变。在某些实施方案中，人IgG1 Fc区包含一个或多个改变抗体糖基化的突变。在某些实施方案中，人IgG1 Fc区包含S298N突变、T299A突变和Y300S突变中的一个或多个。在某些实施方案中，人IgG1 Fc区包含S298N突变、T299A突变和Y300S突变。本文提及的Fc区氨基酸位置基于EU抗体编号。
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白片段包括抗体F(ab)、F(ab')2、Fab'-SH、Fv或scFv片段或由其组成。在某些实施方案中，抗原结合蛋白片段包括抗体F(ab)片段。
抗体F(ab)片段可以用一个或多个血清半衰期延长部分进行修饰。在某些实施方案中，抗体F(ab)片段与对血清白蛋白具有结合特异性的抗原结合蛋白缀合。在某些实施方案中，对血清白蛋白具有结合特异性的抗原结合蛋白是纳米抗体。在某些实施方案中，血清白蛋白是人血清白蛋白或小鼠血清白蛋白。
在某些实施方案中，抗体F(ab)片段包含重链和轻链。在某些实施方案中，F(ab)片段的重链包含本文公开的重链可变区和本文公开的轻链可变区。在某些实施方案中，重链可变区包含以下中的任一个或由其组成：SEQ ID NO:6、8、10、12、14、16、18、20、21、22、23、28、29、30、31、56、57、58、106、107、108、109、110、111、115、116、117、118、119、120、121或112；或与SEQ ID NO:6、8、10、12、14、16、18、20、21、22、23、28、29、30、31、56、57、58、106、107、108、109、110、111、115、116、117、118、119、120、121或112中的任一个具有至少90％、91％、92％、93％、94％、95％、96％、97％、98％或至少99％同一性的序列。在某些实施方案中，轻链可变区包含以下中的任一个或由其组成：SEQ ID NO:7、9、11、13、15、17、19、24、25、26、27、32、33、34、35、59、60、61、112、113、114、123、124、125、126、127、128、129、130、131,或132；或或与SEQ ID NO:7、9、11、13、15、17、19、24、25、26、27、32、33、34、35、59、60、61、112、113、114、123、124、125、126、127、128、129、130、131或132中的任一个具有至少90％、91％、92％、93％、94％、95％、96％、97％、98％或至少99％同一性的序列。
在某些实施方案中，F(ab)片段的重链包含本文公开的重链可变区和重链恒定区或由其组成。在某些实施方案中，重链恒定区源自人IgG1 Fc区、人IgG2 Fc区、人IgG3 Fc区、人IgG4 Fc区或其组合。在某些实施方案中，重链恒定区是人IgG1 Fc区、人IgG2 Fc区、人IgG3 Fc区、人IgG4 Fc区或其组合的片段。在某些实施方案中，重链恒定区包含人IgG Fc区诸如人IgG1 Fc区(SEQ ID NO:54)的前1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、5、36、37、38、39、40、41、44、45、46、7、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98、99、100、101、102、103、104、105、106、107、108、109、110、111、112、113、114、115、116、117、118、119、120、121、122、123、124、125、126、127、128、129、130、131、132、133、134、135、136、137、138、139、140、141、142、143、144、145、146、147、148、149、150、151、152、153、154、155、156、157、158、159、160、161、162、163、164、165、166、167、168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、203、204、205、206、207、208、209、210、211、212、213、214、215、216、217、218、219、220、221、222、223、224,225、226、227、228、229、230、231、232、233、234、235、236、237、238、239、240、241、242、243、244、245、246、247、248、249、250、251、252、253、254、255、256、257、258、259、260、261、262、263、264、265、266、267、268、269、270、271、272、273、274、275、276、277、278、279、280、281、282、283、284、285、286、287、288、289、290、291、292、293、294、295、296、297、298、299或300个氨基酸或由其组成。
在某些实施方案中，F(ab)片段的轻链包含本文公开的轻链可变区和轻链恒定区或由其组成。在某些实施方案中，轻链恒定区源自人卡帕(κ)链、人拉姆达(λ)链或其组合。在某些实施方案中，轻链恒定区包含IgG1轻恒定区的一部分或由其组成。在某些实施方案中，IgG1轻恒定区的一部分包含SEQ ID NO:55的前1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、5、36、37、38、39、40、41、44、45、46、7、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98、99、100、101、102、103、104、105、106或107个氨基酸或由其组成。
在某些实施方案中，F(ab)片段在C端包含一个或多个点突变以减少抗Fab抗体的结合。
在某些实施方案中，抗原结合蛋白包括与小鼠和食蟹猴FGFR3中的一者或两者的交叉反应性。在某些实施方案中，食蟹猴FGFR3由SEQ ID NO:136编码：
ATGGGCGCCCCTGCCTGCGCCCTCGCGCTCTGCGTGGCAGTGGCCATCGTGGCCGGCGCCTCCTCGGAGTCCTTGGGGACGGAGCAGCGCGTCGTGGGGCGAGTGGCAGAAGTGTCCGGCCCGGAGCCCAGCCAGCAGGAGCAGTTGGTCTTCGGCAGCGGGGACGCTGTGGAGCTGAGCTGTCCCCCGCCCGGGGGTGGTCCCATGGGGCCCACTGTCTGGGTCAAGGATGGCGCAGGGCTGGTGCCCTCGGAGCGTGTCCTGGTGGGGCCCCAGCGGCTGCAGGTGCTGAATGCCTCCCACGAGGACTCTGGGGCCTACAGCTGCCGGCAGCGGCTCACACAGCTCGTACTGTGCCACTTCAGTGTGCGGGTGACAGATGCTCCATCCTCGGGAGATGACGAAGACGGGGAGGACGAGGCTGAGGACACAGGTGTGGACACAGGGGCCCCTTACTGGACTCGGCCCGAGCGGATGGACAAGAAGCTGCTGGCTGTGCCGGCCGCCAACACCGTCCGCTTCCGCTGCCCGGCTGCCGGCAACCCCACTCCCTCCATCTCCTGGCTGAAGAATGGCAAGGAGTTCCGCGGCGAGCACCGCATTGGCGGCATCAAGCTTCGGCACCAGCAGTGGAGCCTGGTCATGGAAAGCGTGGTGCCCTCGGACCGCGGCAACTACACCTGCGTGGTGGAGAACAAGTTTGGCAGCATCCGGCAGACATACACGCTGGACGTGCTGGAGCGCTCCCCGCACCGGCCCATCCTGCAGGCGGGGCTGCCGGCCAACCAGACGGCGGTGCTGGGCAGCGATGTGGAGTTTCACTGCAAGGTGTACAGTGATGCGCAGCCCCACATCCAGTGGCTCAAGCACGTGGAGGTGAATGGCAGCAAGGTGGGCCCCGACGGCACACCCTACGTCACCGTGCTCAAGACGGCGGGCGCTAATACCACCGACAAGGAGCTAGAGGTTCTGTCCTTGCACAACGTCACCTTTGAGGACGCCGGGGAGTACACCTGCCTGGCGGGCAATTCTATTGGGTTTTCCCATCACTCTGCGTGGCTCGTGGTGCTGCCAGCTGAGGAGGAGCTGGTGGAGGCTGACGAGGCGGGCAGTGTGTACGCAGGCATCCTCAGCTACGGG
GTGGGCTTCTTCCTGTTCATCCTGGTGGTGGCGGCTGTGACGCTCTGCC
GCCTGCGCAGCACCCCCAAGAAAGGCCTGGGCTCCCCCACCGTGCAC
AAGATCTCCCGCTTCCCACTCAAGCGACAGGTGTCCCTGGAGTCCAAC
GCGTCCATGAGCTCCAACACACCGCTGGTGCGCATCGCAAGGCTGTCC
TCAGGGGAGGGTCCCACACTGGCCAATGTCTCCGAGCTTGAGCTGCCT
GCTGACCCCAAATGGGAGCTGTCTCGGGCCCGGCTGACCCTGGGCAA
GCCCCTTGGGGAGGGCTGCTTTGGCCAGGTGGTCATGGCGGAGGCTAT
CGGCATTGACAAGGACCGGGCCGCCAAGCCTGTCACCGTAGCCGTGA
AGATGCTGAAAGATGATGCCACTGACAAGGACCTGTCAGACCTGGTGT
CTGAGATGGAGATGATGAAGATGATTGGGAAACACAAGAACATTATCA
ACCTGCTGGGCGCCTGCACGCAGGGCGGGCCCCTGTACGTGCTGGTG
GAGTACGCGGCCAAGGGCAACCTGAGGGAGTTTCTGCGGGCGCGGCG
GCCCCCGGGCCTGGACTACTCCTTCGACACCTGCAAGCCGCCTGAGGA
GCAGCTCACCTTCAAGGACCTGGTGTCCTGTGCCTACCAGGTGGCCCG
AGGCATGGAGTACCTCGCCTCCCAGAAGTGCATCCACAGGGACCTGGC
TGCTCGAAATGTGCTGGTGACCGAGGACAACGTGATGAAGATCGCAG
ACTTCGGGCTGGCCCGCGACGTGCACAACCTTGACTACTACAAGAAGA
CAACCAACGGCCGGCTGCCCGTGAAGTGGATGGCGCCTGAGGCCCTG
TTTGACCGAGTCTACACCCACCAGAGTGACGTCTGGTCCTTTGGGGTC
CTGCTCTGGGAGATCTTCACGCTGGGGGGCTCTCCGTACCCCGGCATC
CCTGTGGAGGAGCTCTTCAAGCTGCTGAAGGAGGGTCACCGGATGGA
CAAGCCGGCCAACTGCACACACGACCTGTACATGATCATGCGGGAGTG
CTGGCATGCTGCGCCCTCCCAGAGGCCCACCTTCAAGCAGCTGGTGGA
GGACCTGGACCGTGTCCTCACTGTGACGTCCACCGACGAGTACCTGGA
CCTGTCAGCGCCCTTCGAGCAGTACTCCCCCGGCGGCCAGGACACCCC
GAGCTCCAGCTCCTCAGGGGATGACTCCGTGTTTGCCCACGACCTGCTGCCCCCGGCCCCACCCAGCAGTGGGGGCTCGCGGACGTGA(SEQ ID NO:137)
在某些实施方案中，食蟹猴FGFR3是包含SEQ ID NO:138的IIIc同种型或包含G380R突变(SEQ ID NO:139)的其突变形式：MGAPACALALCVAVAIVAGASSESLGTEQRVVGRVAEVSGPEPSQQEQLVF
GSGDAVELSCPPPGGGPMGPTVWVKDGAGLVPSERVLVGPQRLQVLNAS
HEDSGAYSCRQRLTQLVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTG
APYWTRPERMDKKLLAVPAANTVRFRCPAAGNPTPSISWLKNGKEFRGE
HRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLER
SPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSK
VGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIG
FSHHSAWLVVLPAEEELVEADEAGSVYAGILSYGVGFFLFILVVAAVTLCR
LRSTPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEGP
TLANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRA
AKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQ
GGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSC
AYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNL
DYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGS
PYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFK
QLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDL
LPPAPPSSGGSRT(SEQ ID NO:138)
MGAPACALALCVAVAIVAGASSESLGTEQRVVGRVAEVSGPEPSQQEQLVF
GSGDAVELSCPPPGGGPMGPTVWVKDGAGLVPSERVLVGPQRLQVLNAS
HEDSGAYSCRQRLTQLVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTG
APYWTRPERMDKKLLAVPAANTVRFRCPAAGNPTPSISWLKNGKEFRGE
HRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLER
SPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSK
VGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIG
FSHHSAWLVVLPAEEELVEADEAGSVYAGILSYRVGFFLFILVVAAVTLCR
LRSTPKKGLGSPTVHKISRFPLKRQVSLESNASMSSNTPLVRIARLSSGEGP
TLANVSELELPADPKWELSRARLTLGKPLGEGCFGQVVMAEAIGIDKDRA
AKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKHKNIINLLGACTQ
GGPLYVLVEYAAKGNLREFLRARRPPGLDYSFDTCKPPEEQLTFKDLVSC
AYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNL
DYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGS
PYPGIPVEELFKLLKEGHRMDKPANCTHDLYMIMRECWHAAPSQRPTFK
QLVEDLDRVLTVTSTDEYLDLSAPFEQYSPGGQDTPSSSSSGDDSVFAHDLLPPAPPSSGGSRT(SEQID NO:139)
在某些实施方案中，抗原结合蛋白包含针对FGFR3同种型IIIb和/或同种型IIIc的结合特异性。
在某些实施方案中，抗原结合蛋白与FGFR3特异性结合，并且不与FGFR1、FGFR2和FGFR4中的一种或多种结合，或没有可检测的与FGFR1、FGFR2和FGFR4中的一种或多种的结合。在某些实施方案中，抗原结合蛋白不与FGFR1、FGFR2和FGFR4中的每一种结合，或没有可检测的与FGFR1、FGFR2和FGFR4中的每一种的结合。在某些实施方案中，抗原结合蛋白以约100μM、500μM、1000μM或更大的亲和力与FGFR1、FGFR2和FGFR4中的每一种结合。在某些实施方案中，相对于背景测量，抗原结合蛋白不与FGFR1、FGFR2和FGFR4中的一种或多种结合，如通过Biacore亲和力分析确定。
在某些实施方案中，抗原结合蛋白以约100nM或更小、约90nM或更小、约80nM或更小、约70nM或更小、约60nM或更小、约50nM或更小、约40nM或更小、约30nM或更小、约20nM或更小、约10nM或更小、约9nM或更小、约8nM或更小、约7nM或更小、约6nM或更小、约5nM或更小、约4nM或更小、约3nM或更小、约2.89nM或更小、约2nM或更小、约1.5或更小、约1.4或更小、约1.23或更小、约1.2或更小、或约1nM或更小、约0.8或更小、或约0.6或更小的平衡解离常数(KD)结合人FGFR3。其中的“X nM或更小”包括“小于X nM”的实施方案。其中的“更小”可以意指例如至约2.8nM、至约1.3nM、至约1.1nM、至约0.7nM或至约0.5nM。这些下限可以用于与任何前述上限形成范围，诸如约3nM或<3nM至约2.8nM、约1.5nM或<1.5nM至约1.3nM、约1.3nM或<1.3nM至约1.1nM、约0.9nM或<0.9nM至约0.7nM、或约0.7nM或<0.7nM至约0.5nM。其中的“约X”可以意指例如“X±5％”、“X±4％”、“X±4％”、“X±3％”、“X±2％”、“X±1％”或“X±0.5％”。在某些实施方案中，nM值是如通过表面等离子共振测定诸如Biacore测定获得的。在某些实施方案中，Biacore测定在约4℃、10℃、15℃、20℃、25℃、30℃或37℃下进行。
在某些实施方案中，抗原结合蛋白以约10-2s-1或更小、约5x10-3s-1或更小、约2x10-3 s-1或更小、约10-3s-1或更小、约9x10-4 s-1或更小、约8x10-4s-1或更小、约7x10-4 s-1或更小、约6x10-4 s-1或更小、约5x10-4 s-1或更小、约4x10-4 s-1或更小、或约3.5x10-4 s-1或更小的解离速率(Kd)结合人FGFR3。其中的“更小”可以意指例如至约3x10-4 s-1。其中的“约X”可以意指例如“X±10％”、“X±5％”、“X±4％”、“X±4％”、“X±3％”、“X±2％”、“X±1％”或“X±0.5％”。
在某些实施方案中，抗原结合蛋白以约5μg/ml或更小、约4μg/ml或更小、约3μg/ml或更小、约2μg/ml或更小、约1μg/ml或更小、约0.9μg/ml或更小、约0.8μg/ml或更小、约0.7μg/ml或更小、约0.6μg/ml或更小、约0.5μg/ml或更小、约0.4μg/ml或更小、或约0.3μg/ml或更小的IC50抑制配体诱导的FGFR3二聚化。其中的“更小”可以意指例如至约0.25μg/ml(或更小，例如至约0.2μg/ml或约0.1μg/ml)。其中的“约X”可以意指例如“X±10％”、“X±5％”、“X±4％”、“X±4％”、“X±3％”、“X±2％”、“X±1％”或“X±0.5％”。在某些实施方案中，nM值如通过在约4℃、10℃、15℃、20℃、25℃、30℃或37℃下的同质时间分辨荧光(HTRF)测定获得。
在某些实施方案中，抗原结合蛋白以约5μg/ml或更小、约4μg/ml或更小、约3μg/ml或更小、约2μg/ml或更小、约1μg/ml或更小、约0.9μg/ml或更小、约0.8μg/ml或更小、约0.7μg/ml或更小、约0.6μg/ml或更小、约0.5μg/ml或更小、约0.4μg/ml或更小、或约0.3μg/ml或更小的IC50抑制FGFR3受体激活和下游信号传导。其中的“更小”可以意指例如至约0.25μg/ml(或更小，例如至约0.2μg/ml或约0.1μg/ml)。其中的约X”可以意指例如“X±10％”、“X±5％”、“X±4％”、“X±4％”、“X±3％”、“X±2％”、“X±1％”或“X±0.5％”。％”。在某些实施方案中，nM值如通过同质时间分辨荧光(HTRF)测定获得。
对FGFR3受体激活和下游信号传导的抑制可以通过本领域已知的任何手段确定。在某些实施方案中，对FGFR3受体激活和下游信号传导的抑制通过确定Erk磷酸化来测量。Erk磷酸化的降低指示对FGFR3激活的抑制。Erk磷酸化可以使用同质时间分辨荧光(HTRF)测定确定。在某些实施方案中，测定在软骨细胞中进行。在某些实施方案中，测定在小鼠主肋软骨细胞中进行。
在某些实施方案中，抗原结合蛋白抑制FGFR3G380R突变体的活性。在某些实施方案中，抗原结合蛋白抑制人FGFR3G380R突变体、小鼠FGFR3G380R突变体和/或食蟹猴FGFR3G380R突变体的激活。在某些实施方案中，人FGFR3G380R突变体由SEQ ID NO:133所示的氨基酸序列表示。
在某些实施方案中，抗原结合蛋白或其片段能够穿透骨生长板。
在某些实施方案中，抗原结合蛋白或其片段能够降低在骨生长板中FGFR3与其配体的结合。
抗FGFR3抗原结合蛋白表位
在一个方面，本公开文本提供了一种具有与成纤维细胞生长因子受体3(FGFR3)表位的结合特异性的抗原结合蛋白或其片段，其包含抗体重链可变(VH)结构域和抗体轻链可变(VL)结构域，其中所述抗原结合蛋白结合人FGFR3多肽，其包含下面列举的氨基酸序列SEQ ID NO:134。DTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAGNPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAEEELVE(SEQ ID NO:134)
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白及其抗原结合片段结合人FGFR3多肽，其包含以上列举的氨基酸序列SEQ ID NO:134。以上列举的氨基酸序列对应于FGFR3同种型IIIc的D2D3区，其特异性地针对FGFR3同种型IIIc的氨基酸D143至E365。
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白及其抗原结合片段结合包含以上示出的SEQ ID NO:133的D2区(氨基酸D143至L163)的N端的人FGFR3多肽的表位。
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白及其抗原结合片段结合包含以上示出的SEQ ID NO:133的D2区(氨基酸D143至N170)的N端的人FGFR3多肽的表位。
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白及其抗原结合片段结合包含以上示出的SEQ ID NO:133的D2区(氨基酸D143至D160和G197至L213)的N端和中部的人FGFR3多肽的表位。
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白及其抗原结合片段的一个或多个表位通过氢氘交换(HDX)质谱法确定。HDX通过随时间测量FGFR3上的酰胺氢氘交换来进行。HDX质谱法更详细地描述在
等人(Amino Acids.48:2809-2820.2016)中。
在某些实施方案中，本公开文本的抗FGFR3抗原结合蛋白及其抗原结合片段与参考结合蛋白竞争结合至人FGFR3多肽D2区。
在一个方面，本公开文本提供了一种具有与成纤维细胞生长因子受体3(FGFR3)表位的结合特异性的抗原结合蛋白或其片段，其包含抗体重链可变(VH)结构域和抗体轻链可变(VL)结构域，其中所述抗原结合蛋白与包含选自以下的VH/VL结构域氨基酸序列对的抗体竞争结合至FGFR3：SEQ ID NO:6/SEQ ID NO:7、SEQ ID NO:8/SEQ ID NO:9、SEQ ID NO:10/SEQ ID NO:11、SEQ ID NO:12/SEQ ID NO:13、SEQ ID NO:14/SEQ ID NO:15和SEQ IDNO:16/SEQ ID NO:17。
抗原结合蛋白的表达
在一个方面，提供了编码本文公开的结合蛋白(例如，抗原结合蛋白和其抗原结合片段)的多核苷酸。还提供了制造结合蛋白的方法，其包括表达这些多核苷酸。
将编码本文公开的结合蛋白的多核苷酸典型地插入表达载体，用于引入宿主细胞中，所述宿主细胞可以用于生产希望量的结合蛋白。因此，在某些方面，本公开文本提供了包含本文公开的多核苷酸的表达载体以及包含这些载体和多核苷酸的宿主细胞。
术语“载体”或“表达载体”在本文中用于意指根据本公开文本用作引入细胞中并且在细胞中表达所希望的基因的媒介物的载体。如本领域技术人员所知，此类载体可以容易地选自质粒、噬菌体、病毒和逆转录病毒。一般而言，与本公开文本相容的载体将包含选择标记、促进所希望的基因的克隆的适当的限制性位点，以及进入真核或原核细胞和/或在所述细胞中复制的能力。
出于本公开文本的目的，可以使用许多表达载体系统。例如，一类载体纲利用源自动物病毒诸如牛乳头瘤病毒、多瘤病毒、腺病毒、牛痘病毒、杆状病毒、逆转录病毒(RSV、MMTV或MOMLV)或SV40病毒的DNA元件。其他涉及具有内部核糖体结合位点的多顺反子系统的使用。另外，可以通过引入一种或多种标记物来选择已将DNA整合至其染色体中的细胞，所述一种或多种标记物允许选择转染的宿主细胞。标记物可以针对营养缺陷型宿主的原营养、杀生物剂(例如，抗生素)抗性或对重金属诸如铜的抗性来提供。可选择标记基因可以直接与待表达的DNA序列连接，或通过共转化引入同一细胞中。还可能需要另外的元件来最佳地合成mRNA。这些元件可以包括信号序列、剪接信号以及转录启动子、增强子和终止信号。在一些实施方案中，将克隆的可变区基因与如上所述合成的重链和轻链恒定区基因(例如，人恒定区基因)一起插入表达载体中。
在其他实施方案中，结合蛋白可以使用多顺反子构建体表达。在此类表达系统中，可以从单个多顺反子构建体产生多种目的基因产物，诸如抗体的重链和轻链。这些系统有利地使用内部核糖体进入位点(IRES)以在真核宿主细胞中提供相对高水平的多肽。相容的IRES序列在美国专利号6,193,980中公开，出于所有目的，将其通过引用以其全文并入本文。本领域技术人员将理解，此类表达系统可以用于有效产生本申请中公开的全系列多肽。
更一般地，一旦制备出编码结合蛋白(例如，抗体或其片段)的载体或DNA序列，就可以将表达载体引入适当的宿主细胞中。也就是说，所述宿主细胞可以被转化。可以通过本领域技术人员公知的各种技术来实现将质粒引入宿主细胞中。这些技术包括但不限于转染(包括电泳和电穿孔)、原生质体融合、磷酸钙沉淀、与包膜DNA的细胞融合、显微注射和完整病毒感染。参见Ridgway,A.A.G."Mammalian Expression Vectors"第24.2章,第470-472页Vectors,Rodriguez和Denhardt编辑(Butterworths,Boston,Mass.1988)。可以通过电穿孔将质粒引入宿主中。使转化的细胞在适于产生轻链和重链的条件下生长，并且测定重链和/或轻链蛋白质合成。示例性测定技术包括酶联免疫吸附测定(ELISA)、放射免疫测定(RIA)或荧光激活细胞分选仪分析(FACS)、免疫组织化学等。
如本文所用，术语“转化”应在广义上使用，是指将DNA引入受体宿主细胞中，从而改变基因型。
沿着相同的思路，“宿主细胞”是指已经采用使用重组DNA技术构建的并且编码至少一种异源基因的载体转化的细胞。在描述用于从重组宿主分离多肽的过程时，术语“细胞”和“细胞培养物”可互换使用以表示抗体来源，除非另有明确说明。换言之，从“细胞”中回收多肽可以意指从离心沉淀的全细胞、从裂解细胞培养物的上清液、或从含有培养基和悬浮细胞两者的细胞培养物中回收。
在一个实施方案中，用于抗体表达的宿主细胞系是哺乳动物来源的。本领域技术人员可以确定最适合在其中表达所希望的基因产物的特定宿主细胞系。示例性宿主细胞系包括但不限于DG44和DUXB11(中国仓鼠卵巢系，DHFR-)、HELA(人宫颈癌)、CV-1(猴肾系)、COS(具有SV40 T抗原的CV-1的衍生物)、R1610(中国仓鼠成纤维细胞)、BALBC/3T3(小鼠成纤维细胞)、HEK(人肾系)、SP2/O(小鼠骨髓瘤)、BFA-1c1BPT(牛内皮细胞)、RAJI(人淋巴细胞)、293(人肾)。在一个实施方案中，细胞系提供由其表达的抗体的改变的糖基化，例如无岩藻糖基化(例如，PER.
(Crucell)或FUT8敲除CHO细胞系(
细胞)(Biowa，普林斯顿，新泽西州))。在一个实施方案中，可以使用NS0细胞。CHO细胞是特别有用的。宿主细胞系通常可从商业服务，例如美国组织培养物保藏中心(American TissueCulture Collection)或公开文献的作者获得。
体外生产允许按比例放大以得到大量的所希望的多肽。在组织培养条件下用于哺乳动物细胞培育的技术是本领域已知的并且包括同质悬浮培养(例如，在气升式反应器或连续搅拌反应器中)，或在琼脂糖上微珠或陶瓷盒上的固定化或包埋的细胞培养(例如，在中空纤维、微胶囊中)。如果必要和/或需要的话，可以通过常规色谱方法，例如凝胶过滤、离子交换色谱法、在DEAE-纤维素上的色谱法和/或(免疫)亲和色谱法纯化多肽的溶液。
编码本公开文本所述的结合蛋白的基因也可以在非哺乳动物细胞(诸如细菌或酵母或植物细胞)中表达。在这一方面，应当理解，也可以转化多种单细胞非哺乳动物微生物诸如细菌，即能够在培养或发酵中生长的那些微生物。易于转化的细菌包括肠杆菌科成员，诸如大肠杆菌(Escherichia coli)或沙门氏菌属的菌株；芽孢杆菌科，诸如枯草芽孢杆菌(Bacillus subtilis)；肺炎球菌；链球菌属和流感嗜血杆菌(Haemophilus influenzae)。还应理解，当在细菌中表达时，结合蛋白可以成为内含体的一部分。在一些实施方案中，然后将结合蛋白分离出来、纯化并且组装成功能分子。在一些实施方案中，本公开文本的结合蛋白在细菌宿主细胞中表达。在一些实施方案中，将细菌宿主细胞用包含编码本公开文本的结合蛋白的核酸分子的表达载体转化。
除原核生物外，还可以使用真核微生物。酿酒酵母或普通面包酵母是真核微生物中最常用的，尽管许多其他菌株是通常可获得的。对于在酵母属中的表达，通常使用例如质粒YRp7(Stinchcomb等人,Nature,282:39(1979)；Kingsman等人,Gene,7:141(1979)；Tschemper等人,Gene,10:157(1980))。此质粒已经含有TRP1基因，所述基因提供缺乏在色氨酸中生长的能力的酵母突变菌株的选择标记，例如ATCC号44076或PEP4-1(Jones,Genetics,85:12(1977))。然后，作为酵母宿主细胞基因组的特征的trpl损伤的存在提供通过在没有色氨酸的情况下生长检测转化的有效环境。
制备/施用结合蛋白的方法
还提供了制备结合蛋白(例如，本文公开的抗原结合蛋白和其抗原结合片段)和将其施用于受试者的方法。本公开文本的抗原结合蛋白及其抗原结合片段的施用途径可以是口服、肠胃外、吸入或局部。如本文所用的术语肠胃外包括静脉内、动脉内、腹膜内、肌内、皮下、直肠或阴道施用。虽然所有这些形式的施用明显被认为是在本公开文本的范围内，但施用的形式将是用于注射，例如用于静脉内或动脉内注射或滴注的溶液。通常，适于注射的药物组合物可以包含缓冲液、表面活性剂、任选地稳定剂等。然而，在与本文的传授内容相容的其他方法中，可以将经修饰的抗体直接递送至不良细胞群的位点，由此增加患病组织对治疗剂的暴露。
用于肠胃外施用的制剂包括无菌的水性或非水性溶液、悬浮液和乳液。水性载体包括水、醇/水溶液、乳液或悬浮液，包括盐水和缓冲介质。其他常见的肠胃外媒介物包括磷酸钠溶液、林格氏右旋糖、右旋糖和氯化钠、乳酸林格氏液或固定油。静脉内媒介物包括流体和营养补充剂、电解质补充剂(诸如基于林格氏右旋糖的那些)等。也可以存在防腐剂和其他添加剂，诸如例如抗微生物剂、抗氧化剂、螯合剂和惰性气体等。适合于注射使用的药物组合物包括无菌水溶液(水溶性的)或分散体，以及用于临时制备无菌可注射溶液或分散体的无菌粉末。在这种情况下，所述组合物必须是无菌的并且流动性程度应为存在注射液的可注射性。它应在制造和储存条件下稳定，并且还应防止微生物(诸如细菌和真菌)的污染作用。载体可以是溶剂或分散介质。例如，通过使用包衣、在分散体的情况下通过维持所需粒度、以及通过使用表面活性剂，可以维持适当的流动性。
可以通过各种抗细菌剂和抗真菌剂来实现防止微生物的作用。所述组合物中还可以包含等渗剂，例如糖、多元醇。可以通过在所述组合物中包含延迟吸收的药剂(例如，单硬脂酸铝和明胶)来实现可注射组合物的延长吸收。
在任何情况下，可以通过将活性化合物(例如，经修饰的结合蛋白自身或与其他活性剂组合)以所需的量掺入适当的溶剂中，接着过滤灭菌来制备无菌可注射溶液，所述溶剂具有所枚举的一种成分或多种成分的组合。通常，分散体是通过将活性化合物掺入无菌媒介物中来制备，所述无菌媒介物含有基础分散介质和任何需要的其他成分。在用于制备无菌可注射溶液的无菌粉末的情况下，制备方法通常包括真空干燥和冷冻干燥，所述真空干燥和冷冻干燥由先前无菌过滤的溶液产生活性成分和任何另外的所希望的成分的粉末。将用于注射的制剂加工，填充到容器诸如安瓿、袋、瓶、注射器或小瓶中，并且根据本领域已知的方法在无菌条件下密封。此外，所述制剂可以试剂盒的形式包装和出售。
用于治疗疾病或障碍的本公开文本组合物的有效剂量根据许多不同因素而变化，所述因素包括施用方式、靶部位、受试者的生理状态、受试者是人还是动物、施用的其他药物以及治疗是预防性的还是治疗性的。通常，所述患者是人，但也可以治疗非人哺乳动物，包括转基因哺乳动物。可以滴定治疗剂量以优化安全性和功效。
可以多次施用本文所述的结合蛋白。单剂量之间的间隔可以是每周、每月或每年。间隔也可以是不规则的，如通过测量受试者中结合蛋白或抗原的水平所指示。可替代地，结合蛋白可以作为持续释放配制品施用，在这种情况下需要较不频繁的施用。对于抗体，剂量和频率取决于抗体在患者中的半衰期而改变。通常，人源化抗体显示出最长的半衰期，其次是嵌合抗体和非人抗体。
施用的剂量和频率可以根据治疗是预防性的还是治疗性的而变化。在预防性应用中，将含有本发明结合蛋白的组合物施用至尚未处于疾病状态的受试者，以增强受试者的抵抗力。就软骨发育不全而言，预防性治疗被理解为预防或减轻障碍的一种或多种症状的方法。就癌症而言，预防性治疗被理解为预防癌症发生或减轻癌症的一种或多种症状的方法。将这样的量定义为“预防有效剂量”。在这种用途中，精确量再次取决于受试者的健康状况和一般免疫力。在治疗性应用中，有时需要以相对短的间隔相对高的剂量，直到疾病的进展减少或终止或直到患者显示出疾病症状的部分或完全改善。此后，可以向患者施用预防性方案。
本文所述的结合蛋白可以任选地与有效治疗需要治疗的障碍或病症(例如，预防性或治疗性治疗)的其他药剂一起组合施用。
尽管可以如上所述施用结合蛋白，但必须强调的是，在其他实施方案中，结合蛋白可以作为一线疗法施用于其他健康受试者。在此类实施方案中，可以将结合蛋白施用于尚未经受和未经受一种或多种其他疗法的受试者或已经受或正在经受一种或多种其他疗法的受试者。如本文所用，与辅助疗法结合或组合的结合蛋白(例如，抗体或及其片段)的施用意指依序、同时、同延、并行、伴随或同期施用或应用所述疗法和所公开的结合蛋白。可以定时施用或施加组合的治疗性方案的各种组分以增强治疗的总体有效性。
如前所述，本公开文本的结合蛋白可以以药学有效量施用，以用于哺乳动物障碍的体内治疗。
根据本公开文本的药物组合物通常包括药学上可接受的无毒无菌载体，诸如生理盐水、缓冲液、防腐剂等。出于本申请的目的，结合蛋白的药学有效量应保持意指足以实现与抗原的有效结合并且足以获得益处(例如，足以改善疾病或障碍的症状)的量。当然，本公开文本的药物组合物可以以单剂量或多剂量施用，以提供药学有效量的抗原结合蛋白或其抗原结合片段。
为了与本公开文本的范围保持一致，可以根据本文的治疗方法将抗原结合蛋白或其抗原结合片段以足以产生治疗性或预防性效果的量施用于人或其他动物。本公开文本的结合蛋白可以以通过根据已知技术将结合蛋白与常规药学上可接受的载体或稀释剂组合制备的常规剂型施用于此类人或其他动物。药学上可接受的载体或稀释剂的形式和特征取决于与其组合的活性成分的量，施用的途径和其他公知的变量。在一些实施方案中，包含本公开文本所述的一种或多种结合蛋白的混合剂可以证明是特别有效的。治疗和抑制FGFR3 活性的方法
抗FGFR3抗原结合蛋白或其片段可用于治疗FGFR3介导的疾病或障碍。如本文所用，术语“FGFR3介导的疾病或障碍”是指作为异常FGFR3活性的结果的任何疾病或障碍。在某些实施方案中，疾病或障碍是由FGFR3过度活性或过表达引起的。FGFR3介导的疾病或障碍的非限制性例子包括软骨发育不全、软骨发育不良和癌症。
抗FGFR3抗原结合蛋白或其片段可用于降低FGFR3活性。如本文所用，“FGFR3活性”是指与细胞表面上的FGFR3二聚化相关的任何信号传导事件。FGFR3活性可以是细胞外活性和细胞内活性中的一者或两者。FGFR3活性包括但不限于FGFR3二聚化、细胞外信号调节激酶(Erk)磷酸化、丝裂原激活蛋白激酶激酶(MKK、MEK或MAP2K)磷酸化、FGFR3细胞质酪氨酸激酶结构域活性、和FGF配体结合活性(例如，FGF18与FGFR3的结合)。
如本文所用，术语“软骨发育不全”是指由FGFR3基因突变引起的遗传障碍，所述突变使所得蛋白质过度活性。抗FGFR3抗原结合蛋白或其片段可用于降低软骨发育不全的一种或多种症状。软骨发育不全症状包括但不限于近端肢体缩短、短指(即，短手指和脚趾伴有三叉手)、大头伴有显著前额额部隆起、面中部小伴有鼻梁扁平、脊柱后凸(凸曲度)或脊柱前凸(凹曲度)、内翻(即，弓形腿)或外翻(即，膝外翻、耳部感染(由于咽鼓管阻塞))、睡眠呼吸暂停(中枢性或阻塞性)、和脑积水。软骨发育不全可以通过测量近端肢体长度(例如，股骨和胫骨长度)、手指和脚趾长度、头围(例如，颅骨长度)和腰椎长度中的一种或多种来诊断，尽管可以采用其他解剖学测量。软骨发育不全可以通过基因检测以检测FGFR3基因中的一个或多个突变来诊断。
在一个方面，本公开文本提供了一种用于治疗受试者的FGFR3介导的疾病或障碍的方法，其包括向有需要的受试者施用本文所述的抗原结合蛋白或其片段。
如本文所用，术语“受试者”、“患者”或“个体”是指人或非人动物。术语“非人动物”包括但不限于脊椎动物，诸如非人灵长类动物、绵羊、狗、猫、兔、雪貂、啮齿动物(诸如小鼠、大鼠和豚鼠)、鸟类物种(例如，鸡)、两栖动物和爬行动物。在某些实施方案中，受试者是哺乳动物，诸如非人灵长类动物、绵羊、狗、猫、兔、雪貂或啮齿动物。在某些实施方案中，受试者是食蟹猴。在某些实施方案中，受试者是人。在某些实施方案中，所述受试者是儿童。在某些实施方案中，受试者是青少年。
在某些实施方案中，所述FGFR3介导的疾病或障碍是软骨发育不全。在某些实施方案中，软骨发育不全是FGFR3G380R+软骨发育不全，意指有待治疗的受试者在其FGFR3基因中含有G380R突变，无论是纯合的还是杂合的。
在某些实施方案中，用本文公开的结合蛋白治疗被诊断为患有软骨发育不全或软骨发育不全风险的受试者。在某些实施方案中，与相同发展阶段的未接受所述治疗的对照受试者相比，所述治疗导致选自增加的骨长度(例如，股骨长度和/或胫骨长度)、增加的骨直径(例如，股骨直径)、增加的生长板体积(例如，股骨生长板体积)、增加的椎骨长度、增加的颅骨长度、增加的骨体积、增加的颅骨体积、纠正的椎骨异常(例如，增加的脊柱后凸指数)、和改善的骨龄(例如，更发达的次级骨化中心)的一种或多种作用。
因此，还提供了一种改善受试者的一个或多个骨特征的方法。在某些实施方案中，所述方法包括向有需要的受试者施用本文公开的结合蛋白或其抗原结合片段。在某些实施方案中，改善的骨特征选自骨长度(例如，股骨长度或胫骨长度)、骨直径(例如，股骨直径)、生长板体积、椎骨长度、颅骨长度、骨体积、颅骨体积、脊柱后凸指数、和改善的骨龄。
在某些实施方案中，所述FGFR3介导的疾病或障碍是癌症。在某些实施方案中，所述癌症选自膀胱癌、黑色素瘤、尿路上皮癌和子宫内膜癌。
在另一个方面，本公开文本提供了一种用于治疗受试者的软骨发育不全的方法，其包括向有需要的受试者施用具有与FGFR3表位的结合特异性的抗原结合蛋白或其抗原结合片段，其中所述抗原结合蛋白或其抗原结合片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
在另一个方面，本公开文本提供了一种用于抑制受试者的骨生长板中FGFR3活性和表达中的一者或两者的方法，其包括向受试者施用具有与FGFR3表位的结合特异性的抗原结合蛋白或其抗原结合片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。在某些实施方案中，使用如本文所述的FGFR3抗体。
治疗性和预防性用途
本公开文本提供了具有与FGFR3表位的结合特异性的其结合蛋白或其抗原结合蛋白片段的治疗性用途，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合)，对应于上面公开的治疗方法。例如，本公开文本提供了如本文所述的结合蛋白或其抗原结合蛋白片段，其用于医学。在一些实施方案中，其提供了如本文所述的结合蛋白或其抗原结合蛋白片段，其用作FGFR3活动抑制药剂。在一些实施方案中，其提供了如本文所述的结合蛋白或其抗原结合蛋白片段，其用于治疗FGFR3介导的障碍。本文给出了此类障碍的例子。在一些实施方案中，其提供了如本文所述的结合蛋白或其抗原结合蛋白片段，其用于预防如上例示的软骨发育不全的一种或多种症状。在一些实施方案中，其提供了如本文所述的结合蛋白或其抗原结合蛋白片段，其用于预防如上例示的癌症。本文关于治疗方法、施用、受试者和与疗法和预防相关的所有其他方面所述的实施方案也适用于结合蛋白的这些用途。
本领域技术人员将易于明了，本文所述方法的其他适宜修饰和适应可以在不背离本文所公开实施方案的范围的情况下使用适宜等效方式来进行。虽然现已详细描述某些实施方案，但参照以下实施例将更清楚地理解所述实施方案，所述实施例仅出于说明目的而被包括，并且不旨在限制。
实施例
实施例1-抗FGFR3抗体的产生
免疫原的产生
使用用编码具有突变G380R的全长人FGFR3(SEQ ID NO:133)的DNA(参见图1，GenBank ID NP_000133.1，FGFR3同种型IIIc)转化的300.19前B成淋巴细胞(ATCC，马纳萨斯，弗吉尼亚州)开发抗FGFR3单克隆抗体，所述全长人FGFR3表达在细胞表面上(FGFR3G380R-300.19细胞)。将FGFR3G380R开放阅读框亚克隆到pXL-MCS载体中并且转染到300.19细胞中(免疫原1)。单独地，将编码人FGFR3细胞外结构域(ECD)蛋白(免疫原2)的DNA亚克隆到pTT5载体(Invitrogen)中，并且使用Expi293细胞(Invitrogen)制备。
FGFR3细胞外结构域(ECD)蛋白(免疫原2)：GGLNDIFEAQKIEWHEHHHHHHEDQVDPRLIDGKIQPEPESLGTEQRVVGRAAEVPGPEPGQQEQLVFGSGDAVELSCPPPGGGPMGPTVWVKDGTGLVPSERVLVGPQRLQVLNASHEDSGAYSCRQRLTQRVLCHFSVRVTDAPSSGDDEDGEDEAEDTGVDTGAPYWTRPERMDKKLLAVPAANTVRFRCPAAGNPTPSISWLKNGREFRGEHRIGGIKLRHQQWSLVMESVVPSDRGNYTCVVENKFGSIRQTYTLDVLERSPHRPILQAGLPANQTAVLGSDVEFHCKVYSDAQPHIQWLKHVEVNGSKVGPDGTPYVTVLKTAGANTTDKELEVLSLHNVTFEDAGEYTCLAGNSIGFSHHSAWLVVLPAEEELVEADEAGSAS(SEQ ID NO:140)
通过FACS分析使用在Yin等人(Mol.Cancer Ther.14(10):2270-8.2015)中进一步描述的比较抗体GT184.6.1监测和量化在FGFR3G380R-300.19细胞上的FGFR3表达。使用抗FGFR1(MAB765)、抗FGFR2(MAB6843)、抗FGFR3(MAB766)和抗FGFR4(MAB6852)抗体作为阴性对照(R&D Systems，明尼阿波利斯，明尼苏达州)。使用酶联免疫吸附测定(ELISA)与下文进一步描述的抗体定量FGFR3 ECD蛋白。
将表达FGFR3的细胞维持在补充有热灭活胎牛血清(FBS)(Hyclone)的RPMI(Gibco)中在37℃ 5％ CO2下。通过用补充有5mM EDTA的磷酸盐缓冲(不含Ca-Mg)盐水(CMF-PBS)取代以上培养基并且在该缓冲液中收获细胞来制备用于注射的细胞。通过以500x g离心5分钟使收获的细胞沉淀，通过将沉淀物重悬在CMF-PBS中并且如前所述离心而洗涤一次，计数并且调整至适当的体积(诸如在0.2ml中5x 106个细胞)，通过将细胞沉淀物重悬在CMF-PBS中以用于注射。在处死小鼠之前，FGFR3 ECD蛋白用于加强动物的抗体滴度。
通过将约3-5x 105个细胞/ml接种在T75烧瓶中而将细胞维持在RPMI培养基中，并且生长大约24-48小时，并且用选择抗生素以消除不携带FGFR3质粒的细胞。在用作免疫原之前通过FACS分析验证FGFR3在细胞上的细胞表面表达。
抗FGFR3抗体的产生-杂交瘤策略
将来自Jackson Laboratory(巴尔港，缅因州)的六只八周龄雌性FGFR3 KO(C57BL/6mFGFR3-)小鼠用FGFR3转染细胞(免疫原1)免疫。单独地，将野生型Balb/c小鼠用上述FGFR3 ECD蛋白(免疫原2)免疫。将一组小鼠在第0天用在不含佐剂的PBS中的FGFR3表达细胞(FGFR3G380R-300.19细胞)腹膜内初免，在第14、28、42和56天施用，然后在第77天用在不含佐剂的PBS中的FGFR3 ECD蛋白进行腹膜内加强。每次注射都使用在200μl体积中大约5x106个细胞和在100μl体积PBS中的50μg蛋白质。以两周的间隔进行免疫，并且通过ELISA用FGFR3 ECD蛋白评价IgG滴度以评估免疫反应。
将小鼠处死以收获脾脏，并且放置在培养皿中在37℃下的大约10ml预温热的无血清DMEM(Hyclone)中。用镊子将脾细胞从脾囊中挑出并且转移到15-ml锥形管中。然后用预温热的无血清IMDM(Hyclone)将细胞洗涤三次，并且将来自多只小鼠的细胞合并。
用次黄嘌呤/氨基蝶呤/胸苷(HAT)敏感和IgG非分泌性骨髓瘤细胞系建立融合伴侣细胞F0 B成淋巴细胞(ATCC，马纳萨斯，弗吉尼亚州)用于经免疫的脾细胞。在融合之前，将F0 B成淋巴细胞维持在补充有10％ FBS(37℃，7％ CO2)的IMDM培养基中，确保细胞在融合当天处于对数生长期。
融合方案源自Lerner(Yale J Biol Med,1981,54(5)387-402)和Gefter等人(Somatic Cell Genet,1977,3(2)231-236)。在融合之前，将脾细胞和对数期骨髓瘤细胞用无血清IMDM洗涤三次并且计数。对于每次融合，将1-1.5x 108个脾细胞与2-3x 107个骨髓瘤细胞在50-ml锥形聚丙烯管中混合，并且将细胞用无血清IMDM洗涤一次。脾细胞与骨髓瘤细胞的比率为5:1。将管以500x g离心10分钟以沉淀细胞。吸出上清液后，通过轻敲管底部轻轻重悬沉淀物。然后将管放置在装有37℃水的烧杯中。所有后续融合步骤均在37℃水的烧杯中进行。
接下来，在约1分钟的时程内，将1ml预热至37℃的聚乙二醇1500(PEG)(RocheApplied Science，印第安纳波利斯，印第安纳州)缓慢添加到细胞沉淀物中，同时轻轻摇动管。将细胞在PEG中孵育一分钟，然后在30秒的时程内将1ml无血清IMDM逐滴添加到沉淀物中，并且然后在一分钟内将9ml无血清IMDM添加到沉淀物中。然后将管在室温下以500x g离心10分钟，并且吸出上清液。将沉淀物重悬在200ml过滤的完全杂交瘤生产培养基IMDM(Hyclone)中，所述培养基IMDM补充有10％ FBS(Hyclone)、1x非必需氨基酸(Gibco)、1mM丙酮酸钠(Gibco)、1x pen-strep(Gibco)和1X HAT(Sigma)。然后将重悬的细胞以约200μl/孔的体积接种在十个96孔平底微量滴定板中。将板保持在37℃、7％ CO2的培养箱中。
设计初级杂交瘤筛选以选择产生识别天然FGFR3表位的抗体的杂交瘤克隆。典型地在融合后第10-14天，将来自生长克隆的孔的上清液与稳定表达FGFR3(FGFR3-CHO)的中国仓鼠卵巢(CHO)细胞一起孵育。通过FACS使用荧光标记的山羊抗小鼠二抗检测抗体结合。如果标记的上清液样品在FACS分析中是背景的大于10倍，则认为克隆是阳性的。将选择的阳性克隆转移到24孔平底板中并且扩增用于第二筛选以确认选择。将来自24孔板的上清液与hFGFR3G380R-300.19细胞一起孵育，并且通过荧光标记的山羊抗小鼠二抗进行检测。产生超过4,000个杂交瘤并且通过上述FACS测定进行筛选。只有25个克隆被证实对FGFR3具有特异性。将阳性克隆扩增用于纯化抗体生产、VH和VL基因测序以及冷冻保存。
抗FGFR3抗体的产生-噬菌体展示策略
筛选三个scFv噬菌体文库和两个fab片段噬菌体文库，进行了5次单独的筛选活动。第一活动针对hFGFR3同种型IIIc二聚体筛选scFv噬菌体文库。筛选2,700个scFv抗体，只有13个抗体被鉴定为潜在候选者。第二活动针对hFGFR3同种型IIIc二聚体筛选fab和scFv文库。筛选1,940个抗体，只有13个抗体被鉴定为潜在候选者。第三活动和第四活动针对hFGFR3同种型IIIc二聚体、hFGFR3同种型IIIc his标签单体、和hFGFR3同种型IIIc表达细胞筛选fab和scFv文库。筛选9,770个抗体，只有36个抗体被鉴定为潜在候选者。第五活动针对hFGFR3同种型IIIc单体和小鼠FGFR3(mFGFR3)同种型IIIc单体以及hFGFR3同种型IIIc表达细胞和mFGFR3同种型IIIc表达细胞筛选fab文库。筛选2,990个抗体，只有57个抗体被鉴定为潜在候选者。在五次筛选活动之间，筛选17,400个抗体。在这些筛选的抗体中，发现仅48个在人、小鼠和食蟹猴之间具有交叉反应性，并且发现仅15个阻断FGFR3配体结合。
FGFR家族成员蛋白(人FGFR1αIIIb、FGFR1αIIIc、FGFR1βIIIb、FGFR1βIIIc、FGFR2αIIIc、FGFR2βIIIb、FGFR3 IIIb、FGFR3 IIIc、FGFR4；小鼠FGFR3；和食蟹猴FGFR3重组蛋白)购自R&D Systems(明尼阿波利斯，明尼苏达州)，用于通过ELISA鉴定FGFR3特异性克隆。将编码以下蛋白质的cDNA全部亚克隆到pTT5载体(Invitrogen)中：FGFR3的部分ECD和嵌合ECD蛋白；人FGFR3的人D2D3(hD2D3)和D3(hD3)；小鼠FGFR3的小鼠D2D3(mD2D3)和D3(mD3)；食蟹猴FGFR3的食蟹猴D2D3(cyD2D3)和D3(cyD3)；和hD1-cyD2D3和hD1-mD2D3重组蛋白。使用Lipofectamine2000(Invitrogen)在Expi293细胞(Invitrogen)中通过瞬时转染制备蛋白质。将来自所选克隆的上清液在包被有重组FGFR蛋白的96孔板中孵育，并且用山羊抗小鼠IgG辣根过氧化物酶(Jackson Immunoresearch，西格罗夫，宾夕法尼亚州)检测，然后进行化学发光检测。
用于抗FGFR3抗体的基于细胞的结合测定
使用基于细胞的结合测定来表征以上产生的抗FGFR3抗体。将全长人、小鼠和食蟹猴FGFR3 cDNA亚克隆到不同的pcDNA3.1(Invitrogen)载体中并且转染到300.19细胞(ATCC)中。将FGFR3 Ig结构域D2D3的cDNA亚克隆到pcDNA3.1中并且转染到CHO(D2D3-CHO)(ATCC)细胞中。还将全长人FGFR3G380R、小鼠FGFR3和食蟹猴FGFR3G380R cDNA亚克隆到不同的pcDNA3.1载体中。通过使用Lipofectamine 2000试剂盒(Invitrogen)将人FGFR3G380R、小鼠FGFR3和食蟹猴FGFR3G380R cDNA质粒构建体转染到CHO(hFGFR3G380R-CHO和cyFGFR3G380R-CHO)和人胚胎肾(HEK，mFGFR3-HEK)(ATCC)细胞中来产生表达FGFR3的稳定细胞系。将细胞系维持在补充有10％ FBS的F-12K培养基(对于CHO细胞)和补充有10％ FBS的DMEM(对于HEK细胞)中过夜，然后在遗传霉素(0.5ml/ml)的存在下培养10-14天。挑取分离的单个菌落并且在单独的孔中生长，直到扩增出足够的克隆细胞。使用GT184.6.1通过FACS测定鉴定对遗传霉素具有抗性并且表达高拷贝FGFR3蛋白的稳定克隆。
通过FACS分析获取与在CHO和HEK细胞上表达的野生型FGFR3、突变型FGFR3、和D2D3 FGFR3结合的基于细胞的抗体。将细胞与抗FGFR3抗体在1％牛血清白蛋白的PBS(BPBS)中一起孵育。洗涤三次后，将细胞与荧光缀合的二抗(Invitrogen)一起孵育。
结果表明，若干种抗体与细胞上表达的FGFR3特异性结合。例如，以小鼠和人同种型对照作为阴性对照以及GT184.6.1作为阳性对照，测试克隆KC18、KE35、KE42、KE58、KE63和KE94的与被转染以表达野生型FGFR3、突变型FGFR3、和FGFR3的ECD结构域的CHO、HEK和300.19细胞的结合。所有抗体都与如上所述细胞结合，并且结合谱和滴定动力学相似。阴性对照抗体仅展现出背景反应性。还通过FACS分析观察到抗FGFR3抗体与小鼠原代肋软骨细胞的结合。
还使用GT184.6.1作为阳性对照测试抗体KC18、KE35、KE42、KE58、KE63和KE94的结合特异性。与结合至hFGFR2和hFGFR3两者的GT184.6.1不同，KC18、KE35、KE42、KE58、KE63和KE94仅与hFGFR3结合，表明高的FGFR3特异性。
Biacore亲和力分析
产生带有末端亲和素标签的来自人和小鼠的FGFR3的N端ECD蛋白，并且用于正向形式Biacore测定，其中将蛋白质固定在Biacore芯片上，并且然后确定抗体与芯片上的蛋白质相互作用的动力学。将蛋白质固定在Biacore芯片上大约10,000个响应单位(RU)。然后按照制造商的推荐(GE Healthcare)将抗体暴露于芯片以进行动力学测量。将传感图适于1:1结合模型，并且通过T200评价软件(GE Healthcare)使用双参考扣减进行分析。测试抗体的亲和力在表2中示出。
表2.抗FGFR3抗体的特异性和亲和力
抗FGFR3单克隆抗体的序列分析
在序列分析之前，使用IsoStrip小鼠单克隆抗体Isotyping试剂盒(RocheApplied Science，印第安纳波利斯，印第安纳州)确定每个克隆的同种型。使用5’RACE(cDNA末端快速扩增)试剂盒(Clontech，山景城，加利福尼亚州)按照制造商的说明测序克隆的重(VH)和轻(VL)链可变区。使用RNeasy Miniprep试剂盒根据制造商的说明(Qiagen，日耳曼敦，马里兰州)从每个杂交瘤克隆中提取总RNA。使用5'RACE试剂盒(Clontech)通过聚合酶链反应(PCR)产生含有5'末端的全长第一链cDNA。通过TA克隆试剂盒(Invitrogen)用5’引物(5’RACE试剂盒，Clontech)和IgG同种型特异性重链的3’引物和κ轻链的3’引物的引物扩增VH和VL基因。
IgG1 3’引物：5’-TATGCAAGGCTTACAACCACA-3’(SEQ ID NO:1)
IgG2b 3’引物：5’-GTTAGGAGCTGGGCATTTGTGACACTCC-3’(SEQ ID NO:2)
IgG2c 3’引物：5’-GTTAGGTGCTGGGCATTTGCATGGAGG ACAGGG-3’(SEQ ID NO:3)
IgG3 3’引物：5’-GTTTGGTGGGCATGAAGAACCCGGGG-3’(SEQ ID NO:4)
κ轻链3’引物：5’-CTCATTCCTGTTGAAGCTCTTGAC-3’(SEQ ID NO:5)
将扩增的cDNA克隆到pCR2.1载体(Invitrogen)中，并且使用TOPO-TA克隆试剂盒(Invitrogen)按照制造商的说明进行转化。从2ml LB培养物中分离出质粒，从单个菌落接种并且生长过夜，使用QIAprep spin miniprep试剂盒(Qiagen)，并且使用TOPO-TA克隆试剂盒(Invitrogen)中包含的M13正向和M13反向引物测序。使用IMGT V-Quest网络服务器分析VH和VL基因序列，以鉴定和确认可变区序列。每个抗体的VH和VL序列提供在下表3中：
表3.抗体VH和VL氨基酸序列
以上列举的VH和VL序列的CDR区提供在下表4中：
表4.抗体重链和轻链CDR区
通过抗FGFR3抗体抑制FGF1配体结合
为了测试分离的抗体是否可以抑制FGF1配体与FGFR3之间的结合，进行FGF1配体阻断测定。对于FGFR1配体阻断测定，将人FGFR3细胞FGFR3-300.19和FGFR3G380R-300.19用不同浓度的抗FGFR3抗体和同种型对照预孵育，然后添加人FGF1配体(R&D Systems)。通过FACS测定使用生物素化抗FGF1抗体，然后与链霉亲和素荧光二抗一起孵育来确定hFGF1与细胞上表达的FGFR3的结合。与EC结构域(包括KC18、KE35、KE42、KE58、KE63和KE94)结合的抗FGFR3抗体均阻断FGF1与这些细胞上的FGFR3的结合。
进行使用人和小鼠FGF1配体的基于ELISA的阻断测定。将96孔板的每个孔用人或小鼠FGFR3蛋白包被以捕获抗hFGFR3抗体和/或FGF1配体中的任一者/两者，然后与不同浓度的抗FGFR3抗体和同种型对照一起孵育，然后添加人FGF1配体。通过添加底物以诱导可量化的化学发光反应来确定来FGF1配体的结合。分别通过ELISA检测抗FGFR3抗体对FGF1与人FGFR3和小鼠FGFR3蛋白的结合的抑制。
抗FGFR3抗体的表位分箱
使用Biacore T100(GE Healthcare，皮斯卡塔韦，新泽西州)，将抗FGFR3抗体固定在Biacore CM5芯片上，并且注射FGFR3的ECD蛋白。确定第二抗FGFR3抗体(Ab2)结合至被固定的抗FGFR3抗体(Ab1)捕获的FGFR3蛋白的竞争。将抗FGFR3抗体固定在Biacore芯片上大约100个响应单位(RU)。流通池1保持空白，用于每个芯片上的参考扣减。将在HBS-EP+运行缓冲液中制备的ECD FGFR3蛋白和小鼠抗FGFR3抗体(Ab2)以50μl/min的流速分别注射3分钟和5分钟。在循环之间使用10mM甘氨酸-HCl(pH 2.0)以50μl/min持续1分钟将Ab1表面再生。将传感图适于1:1结合模型，并且通过BiaEvaluation软件(GE Healthcare)使用双参考扣减进行分析。确定的是，抗FGFR3抗体KC18、KE35、KE42、KE58、KE63和KE94竞争在FGFR3上D2结构域周围的相同区域。
还使用氢氘交换(HDX)质谱法以通过测量FGFR3上的酰胺氢氘交换来确定FGFR3上针对这些抗体的表位。HDX质谱法测量随时间的酰胺氢氘交换，并且在0℃和pH 2.5下与蛋白酶消化一起淬灭。简而言之，将有待测试的抗体和抗原混合，使得约90％的抗体在室温下与抗原结合。在中性pH下以10倍稀释到D2O中进行氘交换。然后通过将反应混合物在约0℃至1℃下保持1分钟以还原二硫键来进行淬灭。用蛋白酶XIII和胃蛋白酶进行蛋白酶消化。HDX质谱法更详细地描述在
等人(Amino Acids.48：2809-2820.2016)中。在HDX测定中使用的FGFR3序列列举在下面，并且对应于D2D3区，对应于FGFR3同种型IIIc的D143至E365：
结果(图2)表明KE35和KE58与D2区(D143至L163)的N端结合；KE42与D2区(D143至N170)的N端结合；而KC18、KE94和KE63与D2区(D143至D160和G197至L213)的N端和中部结合。
内化测定
在KMS-11细胞(JCRB细胞库，日本)中评价抗FGFR3抗体的内化。将KMS-11细胞与终浓度为2μg/ml的每种抗体一起孵育30分钟、1、2、5和24小时，然后置于4℃，然后将细胞用PBS(Ca2+和Mg2+)洗涤。将一个亚组的样品用甘氨酸-HCl缓冲液(pH 4)洗涤并且用4％多聚甲醛(Sigma)固定。另一个亚组的样品用Triton X-100(Sigma)进行透化。将具有含有染料和荧光缀合二抗的免疫荧光染色缓冲液的细胞通过PerkinElmer Opera高通量自动显微镜成像，并且使用PerkinE1mer Columbus图像管理系统(PerkinElmer，霍普金顿，马萨诸塞州)进行分析。在用甘氨酸-HCl和Triton X-100处理的KMS-11细胞中观察到抗FGFR3抗体的内化。在未经甘氨酸-HCl和Triton X-100处理的亚组中检测到每个抗体的细胞表面染色(图3)。然后，内化抗体(+pH3/+TX100)的荧光信号与总抗体(-pH3/+TX100)的荧光信号的比率允许比较不同抗体的内化程度(图4)。结果表明抗FGFR3抗体被有效地内化到KMS-11细胞中。
FGFR3二聚化测定
通过化学发光测定评价抗FGFR3抗体对FGFR3二聚化的抑制。由DiscoveRx(弗里蒙特，加利福尼亚州)开发共表达-半乳糖苷酶-prolink(PK)和FGFR3(FGFR3-PK)融合蛋白以及-半乳糖苷酶-酶受体(EA)和FGFR3(FGFR3-EA)融合蛋白的U2OS细胞。β-半乳糖苷酶呈非活性形式，并且当发生二聚化时，prolink和酶受体聚集在一起并且被现在激活的-半乳糖苷酶切割。将细胞与不同浓度的抗FGFR3抗体一起预孵育，然后添加FGF18配体以诱导FGFR3蛋白的二聚化，然后在37℃下孵育过夜。将底物添加到细胞中，并且通过EnVision(PerkinElmer)测量化学发光信号。观察到抗FGFR3抗体对FGFR3二聚化的阻断(图5A-图5C)
人源化
如下产生KC18、KE63和KE94克隆的人源化变体：1)通过来自Chemical ComputingGroup的分子操作环境(Molecular Operating Environment)(MOE)使用KC18-FGFR3复合结构作为模板生成与FGFR3复合的这些抗体的Fv区的结构模型，给出了它们与KC18的高度序列相似性(图6)；2)针对人种系序列搜索VH和VL序列，并且鉴定出最相似的人种系Fv序列和J区。然后将来自KC18、KE63和KE94的CDR移植到最接近的人类种系基因的框架上；3)进行分析以鉴定可能对抗体的FGFR3结合特性很重要的氨基酸。在结构模型中检查后，将选择的韦尼耶区和关键接触残基突变回小鼠残基；以及4)缺失潜在的不利因素(liability)位点。
通过上述方法设计KC18_Hrw1-3和_HV1.69rw2-4的重链以及KC18_Lrw1-3的轻链。进一步分析以引入回复突变、稳定突变和消除其他不需要的基序，鉴定KC18变体的另外重链和轻链，分别为KC18_VH1、VH1b-c、VH2-3、VH3b-c和VH4以及KC18_VL1、VL1b-d、VL2、VL3、VL3b、VL4、VL5和VL6。设计重链KE63 VH1-6和轻链KE63_VL1-4。特别是，设计最初的KE63(KE63_VH1和KE63_VL1)人源化构建体，然后设计对重链和轻链的进一步修饰(KE63_VH2-6和KE63_VL2-4)以引入回复突变、稳定突变并且消除其他不需要的基序。也使用类似的方法来设计KE94人源化构建体KE94_VH1-6。值得注意地，KE63和KE94共用同一套VL设计，即这里的KE63_VL1-4。表5、6和7分别示出了用于配对KC18、KE63和KE94的重链和轻链变体的策略，包括人和小鼠种系同一性百分比。
表5.设计的KC18变体的人和小鼠种系同一性百分比
表6.设计的KE63变体的人和小鼠种系同一性百分比
表7.设计的KE94变体的人和小鼠种系同一性百分比
没有恒定区的KC18、KE64和KE94人源化变体的氨基酸序列描绘在下表8中。没有恒定区的KC18、KE64和KE94人源化变体的核酸序列描绘在下表9中。SEQ ID NO:54和SEQ IDNO:55中分别指示了重和轻恒定区。
表8.KC18、KE64和KE94人源化变体的氨基酸序列
表9.KC18、KE64和KE94人源化变体的核酸序列(HC：重链；LC：轻链)
确定人源化KC18抗体对人和小鼠FGFR3的亲和力并且示出在下表10中。这些人源化抗体的亲和力是与亲本KC18抗体可比较的。
表10.人源化KC18抗体对人和小鼠FGFR3的亲和力
基于KC_Hu18的序列设计人源化抗体KC18_Hu42至KC18_49以进一步去除不利因素位点，诸如FRWH3和CDRH3中的氧化位点、CDRL1中的脱酰胺位点和CDRL2中的氧化位点(表11)。最后，针对VH和VL各自设计两个另外的变体，其导致除KC18_Hu18之外的又8个变体(KC18_Hu42-49)(表12)。
表11.KC18_Hu18中的不利因素基序。使用IMGT定义。不利因素残基在序列中加下划线。
Hu18和新设计的变体(Hu42-49)的序列比对在图7中示出。Hu18残基的突变加下划线。
表12.设计的KC18变体的人和小鼠种系同一性百分比。
表13.设计的KC18变体的氨基酸序列。
表14.设计的KC18变体的序列。
表15.人源化抗FGFR3 Fab片段重链氨基酸序列。
表16.人源化抗FGFR3 Fab片段轻链氨基酸序列。
在某些实施方案中，本申请的抗FGFR3 F(ab)片段包含表15的重链和表16的轻链。
在某些实施方案中，抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:141、164、173、182、191、200、209、218、227、236、245、254、263、272或281，并且抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:142。
在某些实施方案中，抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:143、165、174、183、192、201、210、219、228、237、246、255、264、273或282，并且抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:144。
在某些实施方案中，抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:145、166、175、184、193、202、211、220、229、238、247、256、265、274或283，并且抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:146。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:147、167、176、185、194、203、212、221、230、239、248、257、266、275或284，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:148。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:149、168、177、186、195、204、213、222、231、240、249、258、267、276或285，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:150。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:151、169、178、187、196、205、214、223、232、241、250、259、268、277或286，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:152。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
在某些实施方案中，所述抗体F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
体外分析
针对与FGFR3的结合和特异性筛选抗体。使用同质时间分辨荧光(HTRF)测定使用小鼠原代肋软骨细胞评价对Erk磷酸化的抑制水平来评估活性。简而言之，将从软骨发育不全小鼠模型分离的原代小鼠肋软骨细胞用浓度范围为0.016μg/ml至100μg/ml的抗FGFR3抗体预处理2小时。然后用FGF18刺激细胞5分钟。然后停止反应，使用HTRF测定测量总Erk，并且在单独的HTRF测定中测量磷酸化-Erk(Thr202/Tyr204)。通过取磷酸化-Erk与总Erk的比率并且乘以100来测量Erk磷酸化的抑制百分比。特别地，在HTRF测定中测试小鼠抗体KC18、KE63和KE94及其相应的Fab片段，它们都抑制Erk磷酸化(图9A和图9B)。
为了确定不同小鼠抗体形式对Erk磷酸化抑制的效果，在HTRF测定中测试呈各种形式的KC18小鼠抗体，包括全长抗体(IgG)、Fab、单臂单价抗体(MetMab)和聚乙二醇化(PEG)Fab片段，并且与同种型对照(Iso)进行比较。此外，测试KC18 Fab与半衰期延长(使用人白蛋白纳米抗体(KC18Fab-HLE))，其具有和没有人血清白蛋白(HSA)或小鼠血清白蛋白(MSA)。
全长KC18小鼠抗体具有SEQ ID NO:291的重链(具有mIgG2aFc序列)和SEQ ID NO:292的轻链。KC18小鼠Fab抗体具有SEQ ID NO:293的重链和SEQ ID NO:294的轻链。
QVQLQQSGAELVRPGASVTLSCKASGDTFTDFEIHWVKQTPVHGL
EWIGDIDPETGGTAYNQKFRGRAMLTADRSSSTAYMELRSLTSEDS
AVYYCTRTYDGYPYAMDYWGQGTSVTVSSAKTTAPSVYPLAPVC
GDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDL
YTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEPRGPTIKPCPP
CKCPAPPVAGPSVFIFPPKIKDVLMISLSPIVTCVVVDVSEDDPDVQI
SWFVNNVEVHTAQTQTHREDYNSTLRVVSALPIQHQDWMSGKEF
KCKVNNKGLPSSIERTISKPKGSVRAPQVYVLPPPEEEMTKKQVTL
TCMVTDFMPEDIYVEWTNNGKTELNYKNTEPVLDSDGSYFMYSKLRVEKKNWVERNSYSCSVVHEGLHNHHTTKSFSRTPGK(SEQ ID
NO:291)
DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSNNQKNYLAWYQQ
KPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAEDLAV
YYCQQYYSYRTFGGGTKLEIKRADAAPTVSIFPPSSEQLTSGGASV
VCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMS
STLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC(SEQ ID NO:
292)
QVQLQQSGAELVRPGASVTLSCKASGDTFTDFEIHWVKQTPVHGL
EWIGDIDPETGGTAYNQKFRGRAMLTADRSSSTAYMELRSLTSEDS
AVYYCTRTYDGYPYAMDYWGQGTSVTVSSAKTTAPSVYPLAPVC
GDTTGSSVTLGCLVKGYFPEPVTLTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKI(SEQ ID NO:
293)
DIVMSQSPSSLAVSVGEKVTMSCKSSQSLLYSNNQKNYLAWYQQ
KPGQSPKLLIYWASTRESGVPDRFTGSGSGTDFTLTISSVKAEDLAV
YYCQQYYSYRTFGGGTKLEIKRADAAPTVSIFPPSSEQLTSGGASV
VCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC(SEQ ID NO:
294)
所有形式均抑制Erk磷酸化(图10A至图10C)。在图10A中称为“MetMab”的抗体形式更详细地描述在Merchant等人(PNAS.110(32):E2987-E2996.2013)中。
还在HTRF测定中测试人源化FGFR3抗体，包括Hu18、Hu44和Hu46，并且发现抑制Erk磷酸化(图11)。还确定这些人源化抗体的IC50(分别为图8A至图8C)。
体内分析
为了体内评价抗体，使用软骨发育不全小鼠模型(Ach)。软骨发育不全小鼠是转基因小鼠，其在胶原II启动子的控制下过表达具有G380R突变的小鼠FGFR3蛋白(Shazeeb等人,(2018)Sci Rep 8,469)。将小鼠在1日龄时进行基因分型，并且随机分至对照组(即，盐水)组或抗体给药组。软骨发育不全小鼠(G380R)从3日龄至20日龄每天皮下(SC)接受剂量。然后对小鼠实施安乐死，并且在21日龄时收集骨骼用于显微CT分析。胫骨、股骨、椎骨和颅骨用于分析，并且使用3D显微CT分析测量长度。AMIRA(V6.0.1，FEI，希尔斯伯勒(Hillsboro)，俄勒冈州，美国)用于所有骨骼长度数值分析。使用沿骨骼的种子点和AMIRA中的3D长度工具测量腿骨的长度。结果表明，用KC18 Fab处理的软骨发育不全(Ach)小鼠具有显著增加的胫骨和股骨长度(图12A和图12B)、显著增加的椎骨和颅骨长度(图13A和图13B)、显著增加的脑容量(图14)、和如通过脊柱后凸指数测量的纠正的脊椎异常(图15A-图15B)。用KC18 Fab处理的Ach小鼠还具有若干个改善的骨参数，包括股骨生长板体积和股骨直径(图16A和图16B)。与用媒介物治疗的那些小鼠相比，用KC18 Fab治疗的Ach小鼠还具有改善的骨龄，如胫骨中更发达的次级骨化中心所示(图17)。
总之，由于FGFR3基因的激活突变，软骨发育不全是侏儒症的最常见形式。FGFR3蛋白在生长板中表达，并且其功能是调节适当生长。然而，激活突变导致软骨细胞增殖和分化的过度抑制，这是造成身材矮小和其他骨骼畸形的主要原因。本文产生的抗体对FGFR3具有特异性并且抑制FGFR3活性。抗体的作用机制是抑制配体结合并且阻止受体的激活。本文所述的抗体可以阻断配体激活并且随后抑制下游信号传导，其通过Erk磷酸化的减少来测量。这转化为受体活性的抑制。在Ach小鼠模型中抗FGFR3抗体的体内测试证明了对中轴骨骼和附属骨骼的功效。更具体地，观察到股骨和胫骨长度、颅骨长度以及腰椎长度的显著增加。
序列表
<110> 建新公司(GENZYME CORPORATION)
<120> FGFR3抗体和使用方法
<130> 720727: SA9-231PC
<140>
<141>
<150> 63/068,575
<151> 2020-08-21
<160> 344
<170> PatentIn version 3.5
<210> 1
<211> 21
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成引物"
<400> 1
tatgcaaggc ttacaaccac a 21
<210> 2
<211> 28
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成引物"
<400> 2
gttaggagct gggcatttgt gacactcc 28
<210> 3
<211> 33
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成引物"
<400> 3
gttaggtgct gggcatttgc atggaggaca ggg 33
<210> 4
<211> 26
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成引物"
<400> 4
gtttggtggg catgaagaac ccgggg 26
<210> 5
<211> 24
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成引物"
<400> 5
ctcattcctg ttgaagctct tgac 24
<210> 6
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 6
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 7
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 7
Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 8
<211> 119
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 8
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser
115
<210> 9
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 9
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Lys Phe
20 25 30
Ile Ala Trp Tyr Gln His Lys Pro Gly Lys Gly Pro Arg Leu Leu Ile
35 40 45
His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser Asn Leu Glu Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp Asn Leu Leu Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 10
<211> 119
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 10
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser
115
<210> 11
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 11
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Lys Phe
20 25 30
Ile Ala Trp Tyr Gln His Lys Pro Gly Lys Gly Pro Arg Leu Leu Ile
35 40 45
His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser Asn Leu Glu Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Leu Gln Tyr Asp Asn Leu Leu Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 12
<211> 118
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 12
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser
115
<210> 13
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 13
Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly
1 5 10 15
Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Thr Gly
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ile Leu Thr Ile Arg Ser Val Gln Ala
65 70 75 80
Glu Asp Leu Ala Leu Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Leu
85 90 95
Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys
100 105
<210> 14
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 14
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 15
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 15
Asn Ile Met Met Thr Gln Ser Pro Ser Ser Leu Ala Val Ser Ala Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Ser Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
100 105 110
<210> 16
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 16
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 17
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 17
Asn Ile Met Met Thr Gln Ser Pro Ser Ser Leu Ala Val Ser Ala Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Ser
65 70 75 80
Ile Ser Ser Val Gln Thr Glu Asp Leu Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Ser Tyr Thr Phe Gly Gly Gly Thr Arg Leu Glu Met Lys
100 105 110
<210> 18
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 18
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 19
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 19
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asn Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 20
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 20
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 21
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 21
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 22
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 22
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 23
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 23
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 24
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 24
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Ser Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 25
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 25
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 26
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 26
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asp Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 27
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 27
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asp Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Phe Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 28
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 28
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 29
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 29
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 30
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 30
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 31
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 31
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 32
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 32
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Ser Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 33
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 33
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 34
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 34
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asp Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 35
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 35
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asp Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Phe Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 36
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 36
gaggtacaac ttgtccagtc aggtgcggag gttaaaaaac cgggggccac agttaaactg 60
agctgcaagg ctagcggtga tacttttacc gattttgaga tacactgggt tcagcaggct 120
ccggggaaag ggcttgaatg gattggtgat gttgaccccg aaacgggcgg aaccgcgtat 180
gcagagaagt ttcaaggtag ggcaacgctc actgcggaca gaagcacaga cacggcatac 240
atggagctta gttctctccg ctctgaggat accgctgttt attattgtac tagaacctat 300
gatggatatc catacgcatt cgattattgg gggcaaggga ctcttgtcac agtcagctcc 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 37
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 37
gacatagtga tgactcaatc cccagattca ctcgccgtat cactcggaga aagagccaca 60
attaattgta agagtagtca gtcagtcctt tactctaata acaacaaaaa ttacctggcc 120
tggtaccaac agaaaccagg tcaatctcct aaactgctta tctactgggc tagtacccga 180
gaatcaggag ttcccgatag gttttctggg tctgggagcg gcaccgactt cacactcaca 240
atctctagcg tacaggctga agatgtagcg gtgtattact gccaacagta ttattcatac 300
aggaccttcg gtggtggcac caaagtagaa atcaaacgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 38
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 38
caggtacagt tggtacagtc aggagcggag gttaaaaaac caggggcgtc tgtgaaagtc 60
tcatgtaaag cgagcggaag cacgtttagc gatttcgaga ttcactgggt gagacaagca 120
cccggtcagg gcctggaatg gattggaggg atcgacccgg aaacaggggg tacagcatat 180
aaccaaaagt ttcagggacg ggtcactata acggctgaca ggagcacgtc aactgcgtat 240
atggaattgt ccagtttgag gtcagaagat acggcagtct actactgcac aagaaattat 300
gatggatact ctcaaacgtt tgattattgg ggtcagggga ccctggtaac agtcagctca 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 39
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 39
caggtacagt tggtacagtc aggagcggag gttaaaaaac caggggcgtc tgtgaaagtc 60
tcatgtaaag cgagcggaag cacgtttagc gatttcgaga ttcactgggt gagacaagca 120
cccggtcagg gcctggaatg gattggaggg atcgacccgg aaacaggggg tacagcatat 180
aaccaaaagt ttcagggacg ggtcactata acggctgaca ggagcacgtc aactgcgtat 240
atggaattgt ccagtttgag gtcagaagat acggcagtct actactgcac aagaaattat 300
gatggatact ctcaaacgtt tgattattgg ggtcagggga ccctggtaac agtcagctca 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 40
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 40
caggtacagt tggtacagtc aggagcggag gttaaaaaac caggggcgtc tgtgaaagtc 60
tcatgtaaag cgagcggaag cacgtttagc gatttcgaga ttcactgggt gagacaagca 120
cccggtcagg gcctggaatg gattggaggg atcgacccgg aaacaggggg tacagcatat 180
aaccaaaagt ttcagggacg ggtcactata acggctgaca ggagcacgtc aactgcgtat 240
atggaattgt ccagtttgag gtcagaagat acggcagtct actactgcac aagaaattat 300
gatggatact ctcaaacgtt tgattattgg ggtcagggga ccctggtaac agtcagctca 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 41
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 41
caggtacagt tggtacagtc aggagcggag gttaaaaaac caggggcgtc tgtgaaagtc 60
tcatgtaaag cgagcggaag cacgtttagc gatttcgaga ttcactgggt gagacaagca 120
cccggtcagg gcctggaatg gattggaggg atcgacccgg aaacaggggg tacagcatat 180
aaccaaaagt ttcagggacg ggtcactata acggctgaca ggagcacgtc aactgcgtat 240
atggaattgt ccagtttgag gtcagaagat acggcagtct actactgcac aagaaattat 300
gatggatact ctcaaacgtt tgattattgg ggtcagggga ccctggtaac agtcagctca 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 42
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 42
gatatagtta tgacacagag ccctgactct ctggctgtga gtttgggcga gcgagtaacc 60
attaattgta agagttctca atccgtcctc tactcaagca accagaaaaa ttacctcgcg 120
tggtaccagc aaaaaccagg acagagcccc aaactcttga tctattgggc gtccacccga 180
gagagtggcg tgccagatcg gttttcaggt tctggatctg gtaccgactt cacccttaca 240
atctcaagcc tgcaagcaga ggatgtcgca gtttattatt gccatcagta cctgagcagc 300
tacacattcg gacaaggaac gaaactggaa atcaaacgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 43
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 43
gacatagtaa tgacccaaag tccagattct ttggccgtat ctttgggtga gcgcgttacc 60
atcaactgta agtcttccca gtctgtgttg tactcatcta atcaaaaaaa ctacctcgct 120
tggtaccagc agaagccagg tcaaagcccg aaactgctta tttattgggc gtctacgcga 180
gagtctgggg tccccgatcg gttttcaggg tcaggctctg gcactgattt tactctgact 240
atttcatccc tccaagccga agacgtggca gtgtattact gccaccagta tttgagccct 300
tacacgtttg ggcaggggac taaacttgaa atcaagcgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 44
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 44
gatattgtga tgactcagtc acctgacagt ctggcggttt ctttgggcga aagagtgact 60
ataaattgca aaagcagcca gtcagttctc tattccgaca atcaaaagaa ctatctcgca 120
tggtatcagc agaagccagg gcaatcccca aaattgctta tatactatgc atcaacgcgc 180
gaaagcggtg tacccgatcg gttttcagga agtggcagtg ggaccgactt tacgctgaca 240
atctcttccc ttcaagcgga ggatgtcgcg gtttattatt gtcatcagta tctgagtcct 300
tacacctttg gtcaagggac gaagttggag atcaaacgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 45
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 45
gacatcgtaa tgacccagtc ccccgatagt ctggctgtgt ctttgggcga gagggtaacg 60
ataaactgta aatcaagtca gtcagtgctt tactcagata accagaagaa ctatcttgcg 120
tggtatcagc aaaagcccgg acagtctcca aaacttctta tatatttcgc ttctaccaga 180
gaatcaggtg taccagaccg cttttctgga agcggctctg gtactgactt taccctgaca 240
attagtagct tgcaagctga agatgttgcg gtatattatt gtcaccaata cttgagtccc 300
tatacttttg gccaagggac aaaactggaa ataaagcgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 46
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 46
caggttcagc tggtacaatc tggcgcggaa gtcaaaaagc caggcgcaag tgttaaagtg 60
tcttgcaagg cttcaggatc tacctttaca gattttgaaa tccactgggt aagacaagca 120
cctggccagg ggctggaatg gattggtgcc atagaccctg agacgggagg aaccgcatat 180
aaccagaaat tccaaggtcg agtgactatt actgcggaca agtcaacatc aactgcctat 240
atggagctgt cttctttgag gtcagaggat acagcagttt actactgcac tagaaattac 300
gatggttatt cacggacctt cgattattgg ggtcaaggca ctctggtgac cgtgagttcc 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 47
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 47
caggttcagc tggtacaatc tggcgcggaa gtcaaaaagc caggcgcaag tgttaaagtg 60
tcttgcaagg cttcaggatc tacctttaca gattttgaaa tccactgggt aagacaagca 120
cctggccagg ggctggaatg gattggtgcc atagaccctg agacgggagg aaccgcatat 180
aaccagaaat tccaaggtcg agtgactatt actgcggaca agtcaacatc aactgcctat 240
atggagctgt cttctttgag gtcagaggat acagcagttt actactgcac tagaaattac 300
gatggttatt cacggacctt cgattattgg ggtcaaggca ctctggtgac cgtgagttcc 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 48
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 48
caggttcagc tggtacaatc tggcgcggaa gtcaaaaagc caggcgcaag tgttaaagtg 60
tcttgcaagg cttcaggatc tacctttaca gattttgaaa tccactgggt aagacaagca 120
cctggccagg ggctggaatg gattggtgcc atagaccctg agacgggagg aaccgcatat 180
aaccagaaat tccaaggtcg agtgactatt actgcggaca agtcaacatc aactgcctat 240
atggagctgt cttctttgag gtcagaggat acagcagttt actactgcac tagaaattac 300
gatggttatt cacggacctt cgattattgg ggtcaaggca ctctggtgac cgtgagttcc 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 49
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 49
caggttcagc tggtacaatc tggcgcggaa gtcaaaaagc caggcgcaag tgttaaagtg 60
tcttgcaagg cttcaggatc tacctttaca gattttgaaa tccactgggt aagacaagca 120
cctggccagg ggctggaatg gattggtgcc atagaccctg agacgggagg aaccgcatat 180
aaccagaaat tccaaggtcg agtgactatt actgcggaca agtcaacatc aactgcctat 240
atggagctgt cttctttgag gtcagaggat acagcagttt actactgcac tagaaattac 300
gatggttatt cacggacctt cgattattgg ggtcaaggca ctctggtgac cgtgagttcc 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 50
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 50
gatatagtta tgacacagag ccctgactct ctggctgtga gtttgggcga gcgagtaacc 60
attaattgta agagttctca atccgtcctc tactcaagca accagaaaaa ttacctcgcg 120
tggtaccagc aaaaaccagg acagagcccc aaactcttga tctattgggc gtccacccga 180
gagagtggcg tgccagatcg gttttcaggt tctggatctg gtaccgactt cacccttaca 240
atctcaagcc tgcaagcaga ggatgtcgca gtttattatt gccatcagta cctgagcagc 300
tacacattcg gacaaggaac gaaactggaa atcaaacgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 51
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 51
gacatagtaa tgacccaaag tccagattct ttggccgtat ctttgggtga gcgcgttacc 60
atcaactgta agtcttccca gtctgtgttg tactcatcta atcaaaaaaa ctacctcgct 120
tggtaccagc agaagccagg tcaaagcccg aaactgctta tttattgggc gtctacgcga 180
gagtctgggg tccccgatcg gttttcaggg tcaggctctg gcactgattt tactctgact 240
atttcatccc tccaagccga agacgtggca gtgtattact gccaccagta tttgagccct 300
tacacgtttg ggcaggggac taaacttgaa atcaagcgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 52
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 52
gatattgtga tgactcagtc acctgacagt ctggcggttt ctttgggcga aagagtgact 60
ataaattgca aaagcagcca gtcagttctc tattccgaca atcaaaagaa ctatctcgca 120
tggtatcagc agaagccagg gcaatcccca aaattgctta tatactatgc atcaacgcgc 180
gaaagcggtg tacccgatcg gttttcagga agtggcagtg ggaccgactt tacgctgaca 240
atctcttccc ttcaagcgga ggatgtcgcg gtttattatt gtcatcagta tctgagtcct 300
tacacctttg gtcaagggac gaagttggag atcaaacgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 53
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 53
gacatcgtaa tgacccagtc ccccgatagt ctggctgtgt ctttgggcga gagggtaacg 60
ataaactgta aatcaagtca gtcagtgctt tactcagata accagaagaa ctatcttgcg 120
tggtatcagc aaaagcccgg acagtctcca aaacttctta tatatttcgc ttctaccaga 180
gaatcaggtg taccagaccg cttttctgga agcggctctg gtactgactt taccctgaca 240
attagtagct tgcaagctga agatgttgcg gtatattatt gtcaccaata cttgagtccc 300
tatacttttg gccaagggac aaaactggaa ataaagcgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 54
<211> 329
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 54
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
115 120 125
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
130 135 140
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
145 150 155 160
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
165 170 175
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
180 185 190
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
195 200 205
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
210 215 220
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
225 230 235 240
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
245 250 255
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
260 265 270
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
290 295 300
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
305 310 315 320
Gln Lys Ser Leu Ser Leu Ser Pro Gly
325
<210> 55
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 55
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
1 5 10 15
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
20 25 30
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
35 40 45
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
50 55 60
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
65 70 75 80
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
85 90 95
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
100 105
<210> 56
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 56
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 57
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 57
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 58
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 58
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 59
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 59
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asn Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 60
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 60
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asp Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 61
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 61
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asp Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Phe Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 62
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 62
gaggttcagt tggtgcaaag tggggccgag gttaaaaaac caggtgcaac cgtgaaactg 60
tcctgcaagg cgagtggtga tacatttaca gattttgaaa ttcattgggt acagcaggca 120
cccggaaagg gattggaatg gataggagat gtggacccgg agactggcgg aaccgcgtac 180
gcggagaaat ttcagggcag agccactttg acggcggata gaagtacgga tactgcctac 240
cttgaactga gttccttgcg gtccgaagat acggcagttt actattgtac tcgcacgtat 300
gatggctacc catacgcttt cgattattgg ggacaaggca ctctcgtgac cgtatcttca 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 63
<211> 449
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 63
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly
<210> 64
<211> 1347
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 64
gaggttcagt tggtgcaaag tggggccgag gttaaaaaac caggtgcaac cgtgaaactg 60
tcctgcaagg cgagtggtga tacatttaca gattttgaaa ttcattgggt acagcaggca 120
cccggaaagg gattggaatg gataggagat gtggacccgg agactggcgg aaccgcgtac 180
gcggagaaat ttcagggcag agccactttg acggcggata gaagtacgga tactgcctac 240
cttgaactga gttccttgcg gtccgaagat acggcagttt actattgtac tcgcacgtat 300
gatggctacc catacgcttt cgattattgg ggacaaggca ctctcgtgac cgtatcttca 360
gcttcaacca agggaccttc tgtctttcct ctggcccctt caagcaagag cacttccgga 420
gggactgccg cactcgggtg ccttgtgaaa gattacttcc cagagcctgt caccgtcagc 480
tggaattcag gcgctctgac tagcggagtg cacaccttcc ccgctgtgct tcagtcctcc 540
ggactctact ctctgagcag cgtggtgacc gtgccgtcct cttctctggg gacccagact 600
tatatctgca acgtcaatca taagccttct aataccaagg tggacaagaa ggtggaaccc 660
aaatcatgtg acaagaccca cacctgtccg ccctgtccgg cacccgaact gctgggtggc 720
ccttccgtgt tccttttccc tccaaagccg aaggacactc ttatgatttc tcgcactccc 780
gaagtgactt gcgtcgtggt ggatgtgtcc catgaggatc cagaggtcaa gttcaactgg 840
tacgtggacg gtgtggaagt ccacaacgcc aagactaagc cgagagagga acagtacaat 900
tcaacctatc gggtggtgag cgtcctgacc gtgctgcacc aggactggct taacggaaag 960
gagtacaagt gcaaagtgtc aaacaaggca ctgcccgctc cgatcgaaaa gaccattagc 1020
aaagctaagg gccagcccag agaaccccaa gtctataccc ttccacccag ccgggacgag 1080
ctgaccaaaa accaggtgtc actcacttgt ctcgtgaagg gtttctaccc ctcagacatc 1140
gccgtcgaat gggagtccaa tggtcagcca gagaacaact acaaaaccac ccctcccgtg 1200
ctggacagcg acgggtcttt ctttctctac tcaaagctga ccgtggataa gtctcgctgg 1260
cagcaaggga atgtgttttc ctgttcagtg atgcatgagg cccttcataa tcattacacc 1320
caaaagtcac tgagcctgtc tcccgga 1347
<210> 65
<211> 449
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 65
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly
<210> 66
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 66
gacattgtaa tgacacaatc tcccgactct cttgcagtca gcttgggtga acgagcaact 60
ataaattgta aaagcagcca gtctgtactc tactctaata acaacaagaa ctacctcgca 120
tggtatcagc agaaaccggg gcaaagtcct aaacttttga tctattgggc aagtaccagg 180
gagagcggag tacccgacag attcagcggg tctggatcag gcaccgattt tactctcacc 240
atttcttcag ttcaagctga agacgtcgca gtctactact gccagcagta ttacagttac 300
cgaacttttg gcggtggaac aaaagtggaa ataaagcgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 67
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 67
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asn Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 68
<211> 657
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多核苷酸"
<400> 68
gacatagtta tgacccagtc tccagactcc ctcgcagttt ctctcggcga gagagtaaca 60
atcaactgta agtcatcaca gtccgtactc tactctgaca accaaaagaa ttatttggct 120
tggtatcagc aaaagccagg acaaagcccc aaacttctta tctattttgc cagcactagg 180
gagtccgggg tacccgaccg ctttagtggc tcaggttctg ggacagactt tacactgacc 240
atttctagcg tacaggctga agacgttgca gtctactact gccagcaata ctattcttac 300
agaacgtttg gcgggggcac aaagttggag atcaaacgca ctgtggcagc cccttctgtg 360
tttatcttcc caccctccga cgagcagctc aagtccggta ccgcctctgt cgtctgcctg 420
ctgaacaatt tctacccaag agaggccaag gtgcagtgga aggtggacaa cgcactgcaa 480
agcggtaatt cacaagagtc agtcaccgaa caagactcaa aggacagcac ctactcactg 540
tcatccaccc tgactctctc aaaggctgac tacgaaaagc acaaagtgta tgcttgtgaa 600
gtcactcatc agggcctttc tagccctgtg accaagagct tcaacagagg cgaatgc 657
<210> 69
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 69
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asp Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Phe Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 70
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 70
Gly Asp Thr Phe Thr Asp Phe Glu
1 5
<210> 71
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 71
Ile Asp Pro Glu Thr Gly Gly Thr
1 5
<210> 72
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 72
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr
1 5 10
<210> 73
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 73
Gln Ser Leu Leu Tyr Ser Asn Asn Gln Lys Asn Tyr
1 5 10
<210> 74
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 74
Trp Ala Ser
1
<210> 75
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 75
Gln Gln Tyr Tyr Ser Tyr Arg Thr
1 5
<210> 76
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 76
Gly Tyr Thr Phe Thr Asp Tyr Asn
1 5
<210> 77
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 77
Ile Asn Pro Asn Asn Gly Gly Thr
1 5
<210> 78
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 78
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr
1 5 10
<210> 79
<211> 6
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 79
Gln Asp Ile Asn Lys Phe
1 5
<210> 80
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 80
Tyr Thr Ser
1
<210> 81
<211> 9
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 81
Leu Gln Tyr Asp Asn Leu Leu Trp Thr
1 5
<210> 82
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 82
Gly Tyr Thr Phe Thr Asp Tyr Asn
1 5
<210> 83
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 83
Ile Asn Pro Asn Asn Gly Gly Thr
1 5
<210> 84
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 84
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe
1 5 10
<210> 85
<211> 6
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 85
Gln Asp Ile Asn Lys Phe
1 5
<210> 86
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 86
Tyr Thr Ser
1
<210> 87
<211> 9
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 87
Leu Gln Tyr Asp Asn Leu Leu Trp Thr
1 5
<210> 88
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 88
Gly Tyr Thr Val Thr Asp Tyr Tyr
1 5
<210> 89
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 89
Ile Asn Pro Asn Asn Gly Val Thr
1 5
<210> 90
<211> 11
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 90
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr
1 5 10
<210> 91
<211> 6
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 91
Gln Asp Val Ser Thr Gly
1 5
<210> 92
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 92
Trp Ala Ser
1
<210> 93
<211> 9
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 93
Gln Gln His Tyr Ser Thr Pro Leu Thr
1 5
<210> 94
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 94
Gly Ser Thr Phe Ser Asp Phe Glu
1 5
<210> 95
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 95
Ile Asp Pro Glu Thr Gly Gly Thr
1 5
<210> 96
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 96
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr
1 5 10
<210> 97
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 97
Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Asn Tyr
1 5 10
<210> 98
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 98
Trp Ala Ser
1
<210> 99
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 99
His Gln Tyr Leu Ser Ser Tyr Thr
1 5
<210> 100
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 100
Gly Ser Thr Phe Thr Asp Phe Glu
1 5
<210> 101
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 101
Ile Asp Pro Glu Thr Gly Gly Thr
1 5
<210> 102
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 102
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr
1 5 10
<210> 103
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 103
Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Asn Tyr
1 5 10
<210> 104
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 104
Trp Ala Ser
1
<210> 105
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 105
His Gln Tyr Leu Ser Ser Tyr Thr
1 5
<210> 106
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 106
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Ser Thr Ser Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 107
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 107
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Tyr
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Ser Thr Ser Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 108
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 108
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Tyr
20 25 30
Glu Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Ser Thr Ser Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 109
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 109
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 110
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 110
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Glu Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 111
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 111
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 112
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 112
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 113
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 113
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 114
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 114
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asn Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 115
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 115
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 116
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 116
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 117
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 117
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Glu Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Ala Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Val Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 118
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 118
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 119
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 119
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Ser Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Arg Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 120
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 120
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Ser Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Arg Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 121
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 121
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Glu Pro Glu Ser Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Arg Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Ala Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Val Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 122
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 122
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 123
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 123
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 124
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 124
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 125
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 125
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 126
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 126
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 127
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 127
Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Met Asn Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 128
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 128
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Val Gly
1 5 10 15
Glu Pro Val Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Leu Gln Lys Pro Gly Gln
35 40 45
Ser Pro Gln Leu Leu Ile Tyr Trp Gly Ser Thr Arg Ala Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
65 70 75 80
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 129
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 129
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Val Gly
1 5 10 15
Glu Pro Val Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Leu Gln Lys Pro Gly Gln
35 40 45
Ser Pro Gln Leu Leu Ile Tyr Trp Gly Ser Thr Arg Ala Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
65 70 75 80
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 130
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 130
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Ala Val Thr Val Gly
1 5 10 15
Glu Lys Val Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Gly Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 131
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 131
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Val Gly
1 5 10 15
Asp Arg Val Thr Met Thr Cys Arg Ala Ser Gln Gly Ile Ser Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 132
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 132
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Val Gly
1 5 10 15
Asp Arg Val Thr Met Thr Cys Arg Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Gln Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
<210> 133
<211> 806
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 133
Met Gly Ala Pro Ala Cys Ala Leu Ala Leu Cys Val Ala Val Ala Ile
1 5 10 15
Val Ala Gly Ala Ser Ser Glu Ser Leu Gly Thr Glu Gln Arg Val Val
20 25 30
Gly Arg Ala Ala Glu Val Pro Gly Pro Glu Pro Gly Gln Gln Glu Gln
35 40 45
Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser Cys Pro Pro Pro
50 55 60
Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val Lys Asp Gly Thr Gly
65 70 75 80
Leu Val Pro Ser Glu Arg Val Leu Val Gly Pro Gln Arg Leu Gln Val
85 90 95
Leu Asn Ala Ser His Glu Asp Ser Gly Ala Tyr Ser Cys Arg Gln Arg
100 105 110
Leu Thr Gln Arg Val Leu Cys His Phe Ser Val Arg Val Thr Asp Ala
115 120 125
Pro Ser Ser Gly Asp Asp Glu Asp Gly Glu Asp Glu Ala Glu Asp Thr
130 135 140
Gly Val Asp Thr Gly Ala Pro Tyr Trp Thr Arg Pro Glu Arg Met Asp
145 150 155 160
Lys Lys Leu Leu Ala Val Pro Ala Ala Asn Thr Val Arg Phe Arg Cys
165 170 175
Pro Ala Ala Gly Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn Gly
180 185 190
Arg Glu Phe Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg His
195 200 205
Gln Gln Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly
210 215 220
Asn Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr
225 230 235 240
Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu Gln
245 250 255
Ala Gly Leu Pro Ala Asn Gln Thr Ala Val Leu Gly Ser Asp Val Glu
260 265 270
Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp Leu
275 280 285
Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro Asp Gly Thr Pro
290 295 300
Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn Thr Thr Asp Lys Glu
305 310 315 320
Leu Glu Val Leu Ser Leu His Asn Val Thr Phe Glu Asp Ala Gly Glu
325 330 335
Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Phe Ser His His Ser Ala
340 345 350
Trp Leu Val Val Leu Pro Ala Glu Glu Glu Leu Val Glu Ala Asp Glu
355 360 365
Ala Gly Ser Val Tyr Ala Gly Ile Leu Ser Tyr Arg Val Gly Phe Phe
370 375 380
Leu Phe Ile Leu Val Val Ala Ala Val Thr Leu Cys Arg Leu Arg Ser
385 390 395 400
Pro Pro Lys Lys Gly Leu Gly Ser Pro Thr Val His Lys Ile Ser Arg
405 410 415
Phe Pro Leu Lys Arg Gln Val Ser Leu Glu Ser Asn Ala Ser Met Ser
420 425 430
Ser Asn Thr Pro Leu Val Arg Ile Ala Arg Leu Ser Ser Gly Glu Gly
435 440 445
Pro Thr Leu Ala Asn Val Ser Glu Leu Glu Leu Pro Ala Asp Pro Lys
450 455 460
Trp Glu Leu Ser Arg Ala Arg Leu Thr Leu Gly Lys Pro Leu Gly Glu
465 470 475 480
Gly Cys Phe Gly Gln Val Val Met Ala Glu Ala Ile Gly Ile Asp Lys
485 490 495
Asp Arg Ala Ala Lys Pro Val Thr Val Ala Val Lys Met Leu Lys Asp
500 505 510
Asp Ala Thr Asp Lys Asp Leu Ser Asp Leu Val Ser Glu Met Glu Met
515 520 525
Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn Leu Leu Gly Ala
530 535 540
Cys Thr Gln Gly Gly Pro Leu Tyr Val Leu Val Glu Tyr Ala Ala Lys
545 550 555 560
Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg Arg Pro Pro Gly Leu Asp
565 570 575
Tyr Ser Phe Asp Thr Cys Lys Pro Pro Glu Glu Gln Leu Thr Phe Lys
580 585 590
Asp Leu Val Ser Cys Ala Tyr Gln Val Ala Arg Gly Met Glu Tyr Leu
595 600 605
Ala Ser Gln Lys Cys Ile His Arg Asp Leu Ala Ala Arg Asn Val Leu
610 615 620
Val Thr Glu Asp Asn Val Met Lys Ile Ala Asp Phe Gly Leu Ala Arg
625 630 635 640
Asp Val His Asn Leu Asp Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu
645 650 655
Pro Val Lys Trp Met Ala Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr
660 665 670
His Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Phe
675 680 685
Thr Leu Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe
690 695 700
Lys Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro Ala Asn Cys Thr
705 710 715 720
His Asp Leu Tyr Met Ile Met Arg Glu Cys Trp His Ala Ala Pro Ser
725 730 735
Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu Asp Arg Val Leu
740 745 750
Thr Val Thr Ser Thr Asp Glu Tyr Leu Asp Leu Ser Ala Pro Phe Glu
755 760 765
Gln Tyr Ser Pro Gly Gly Gln Asp Thr Pro Ser Ser Ser Ser Ser Gly
770 775 780
Asp Asp Ser Val Phe Ala His Asp Leu Leu Pro Pro Ala Pro Pro Ser
785 790 795 800
Ser Gly Gly Ser Arg Thr
805
<210> 134
<211> 223
<212> PRT
<213> 智人
<400> 134
Asp Thr Gly Val Asp Thr Gly Ala Pro Tyr Trp Thr Arg Pro Glu Arg
1 5 10 15
Met Asp Lys Lys Leu Leu Ala Val Pro Ala Ala Asn Thr Val Arg Phe
20 25 30
Arg Cys Pro Ala Ala Gly Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys
35 40 45
Asn Gly Arg Glu Phe Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu
50 55 60
Arg His Gln Gln Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp
65 70 75 80
Arg Gly Asn Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg
85 90 95
Gln Thr Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile
100 105 110
Leu Gln Ala Gly Leu Pro Ala Asn Gln Thr Ala Val Leu Gly Ser Asp
115 120 125
Val Glu Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile Gln
130 135 140
Trp Leu Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro Asp Gly
145 150 155 160
Thr Pro Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn Thr Thr Asp
165 170 175
Lys Glu Leu Glu Val Leu Ser Leu His Asn Val Thr Phe Glu Asp Ala
180 185 190
Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Phe Ser His His
195 200 205
Ser Ala Trp Leu Val Val Leu Pro Ala Glu Glu Glu Leu Val Glu
210 215 220
<210> 135
<211> 806
<212> PRT
<213> 智人
<400> 135
Met Gly Ala Pro Ala Cys Ala Leu Ala Leu Cys Val Ala Val Ala Ile
1 5 10 15
Val Ala Gly Ala Ser Ser Glu Ser Leu Gly Thr Glu Gln Arg Val Val
20 25 30
Gly Arg Ala Ala Glu Val Pro Gly Pro Glu Pro Gly Gln Gln Glu Gln
35 40 45
Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser Cys Pro Pro Pro
50 55 60
Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val Lys Asp Gly Thr Gly
65 70 75 80
Leu Val Pro Ser Glu Arg Val Leu Val Gly Pro Gln Arg Leu Gln Val
85 90 95
Leu Asn Ala Ser His Glu Asp Ser Gly Ala Tyr Ser Cys Arg Gln Arg
100 105 110
Leu Thr Gln Arg Val Leu Cys His Phe Ser Val Arg Val Thr Asp Ala
115 120 125
Pro Ser Ser Gly Asp Asp Glu Asp Gly Glu Asp Glu Ala Glu Asp Thr
130 135 140
Gly Val Asp Thr Gly Ala Pro Tyr Trp Thr Arg Pro Glu Arg Met Asp
145 150 155 160
Lys Lys Leu Leu Ala Val Pro Ala Ala Asn Thr Val Arg Phe Arg Cys
165 170 175
Pro Ala Ala Gly Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn Gly
180 185 190
Arg Glu Phe Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg His
195 200 205
Gln Gln Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly
210 215 220
Asn Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr
225 230 235 240
Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu Gln
245 250 255
Ala Gly Leu Pro Ala Asn Gln Thr Ala Val Leu Gly Ser Asp Val Glu
260 265 270
Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp Leu
275 280 285
Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro Asp Gly Thr Pro
290 295 300
Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn Thr Thr Asp Lys Glu
305 310 315 320
Leu Glu Val Leu Ser Leu His Asn Val Thr Phe Glu Asp Ala Gly Glu
325 330 335
Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Phe Ser His His Ser Ala
340 345 350
Trp Leu Val Val Leu Pro Ala Glu Glu Glu Leu Val Glu Ala Asp Glu
355 360 365
Ala Gly Ser Val Tyr Ala Gly Ile Leu Ser Tyr Gly Val Gly Phe Phe
370 375 380
Leu Phe Ile Leu Val Val Ala Ala Val Thr Leu Cys Arg Leu Arg Ser
385 390 395 400
Pro Pro Lys Lys Gly Leu Gly Ser Pro Thr Val His Lys Ile Ser Arg
405 410 415
Phe Pro Leu Lys Arg Gln Val Ser Leu Glu Ser Asn Ala Ser Met Ser
420 425 430
Ser Asn Thr Pro Leu Val Arg Ile Ala Arg Leu Ser Ser Gly Glu Gly
435 440 445
Pro Thr Leu Ala Asn Val Ser Glu Leu Glu Leu Pro Ala Asp Pro Lys
450 455 460
Trp Glu Leu Ser Arg Ala Arg Leu Thr Leu Gly Lys Pro Leu Gly Glu
465 470 475 480
Gly Cys Phe Gly Gln Val Val Met Ala Glu Ala Ile Gly Ile Asp Lys
485 490 495
Asp Arg Ala Ala Lys Pro Val Thr Val Ala Val Lys Met Leu Lys Asp
500 505 510
Asp Ala Thr Asp Lys Asp Leu Ser Asp Leu Val Ser Glu Met Glu Met
515 520 525
Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn Leu Leu Gly Ala
530 535 540
Cys Thr Gln Gly Gly Pro Leu Tyr Val Leu Val Glu Tyr Ala Ala Lys
545 550 555 560
Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg Arg Pro Pro Gly Leu Asp
565 570 575
Tyr Ser Phe Asp Thr Cys Lys Pro Pro Glu Glu Gln Leu Thr Phe Lys
580 585 590
Asp Leu Val Ser Cys Ala Tyr Gln Val Ala Arg Gly Met Glu Tyr Leu
595 600 605
Ala Ser Gln Lys Cys Ile His Arg Asp Leu Ala Ala Arg Asn Val Leu
610 615 620
Val Thr Glu Asp Asn Val Met Lys Ile Ala Asp Phe Gly Leu Ala Arg
625 630 635 640
Asp Val His Asn Leu Asp Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu
645 650 655
Pro Val Lys Trp Met Ala Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr
660 665 670
His Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Phe
675 680 685
Thr Leu Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe
690 695 700
Lys Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro Ala Asn Cys Thr
705 710 715 720
His Asp Leu Tyr Met Ile Met Arg Glu Cys Trp His Ala Ala Pro Ser
725 730 735
Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu Asp Arg Val Leu
740 745 750
Thr Val Thr Ser Thr Asp Glu Tyr Leu Asp Leu Ser Ala Pro Phe Glu
755 760 765
Gln Tyr Ser Pro Gly Gly Gln Asp Thr Pro Ser Ser Ser Ser Ser Gly
770 775 780
Asp Asp Ser Val Phe Ala His Asp Leu Leu Pro Pro Ala Pro Pro Ser
785 790 795 800
Ser Gly Gly Ser Arg Thr
805
<210> 136
<211> 2421
<212> DNA
<213> Macaca fascicularis
<400> 136
atgggcgccc ctgcctgcgc cctcgcgctc tgcgtggcag tggccatcgt ggccggcgcc 60
tcctcggagt ccttggggac ggagcagcgc gtcgtggggc gagtggcaga agtgtccggc 120
ccggagccca gccagcagga gcagttggtc ttcggcagcg gggacgctgt ggagctgagc 180
tgtcccccgc ccgggggtgg tcccatgggg cccactgtct gggtcaagga tggcgcaggg 240
ctggtgccct cggagcgtgt cctggtgggg ccccagcggc tgcaggtgct gaatgcctcc 300
cacgaggact ctggggccta cagctgccgg cagcggctca cacagctcgt actgtgccac 360
ttcagtgtgc gggtgacaga tgctccatcc tcgggagatg acgaagacgg ggaggacgag 420
gctgaggaca caggtgtgga cacaggggcc ccttactgga ctcggcccga gcggatggac 480
aagaagctgc tggctgtgcc ggccgccaac accgtccgct tccgctgccc ggctgccggc 540
aaccccactc cctccatctc ctggctgaag aatggcaagg agttccgcgg cgagcaccgc 600
attggcggca tcaagcttcg gcaccagcag tggagcctgg tcatggaaag cgtggtgccc 660
tcggaccgcg gcaactacac ctgcgtggtg gagaacaagt ttggcagcat ccggcagaca 720
tacacgctgg acgtgctgga gcgctccccg caccggccca tcctgcaggc ggggctgccg 780
gccaaccaga cggcggtgct gggcagcgat gtggagtttc actgcaaggt gtacagtgat 840
gcgcagcccc acatccagtg gctcaagcac gtggaggtga atggcagcaa ggtgggcccc 900
gacggcacac cctacgtcac cgtgctcaag acggcgggcg ctaataccac cgacaaggag 960
ctagaggttc tgtccttgca caacgtcacc tttgaggacg ccggggagta cacctgcctg 1020
gcgggcaatt ctattgggtt ttcccatcac tctgcgtggc tcgtggtgct gccagctgag 1080
gaggagctgg tggaggctga cgaggcgggc agtgtgtacg caggcatcct cagctacggg 1140
gtgggcttct tcctgttcat cctggtggtg gcggctgtga cgctctgccg cctgcgcagc 1200
acccccaaga aaggcctggg ctcccccacc gtgcacaaga tctcccgctt cccactcaag 1260
cgacaggtgt ccctggagtc caacgcgtcc atgagctcca acacaccgct ggtgcgcatc 1320
gcaaggctgt cctcagggga gggtcccaca ctggccaatg tctccgagct tgagctgcct 1380
gctgacccca aatgggagct gtctcgggcc cggctgaccc tgggcaagcc ccttggggag 1440
ggctgctttg gccaggtggt catggcggag gctatcggca ttgacaagga ccgggccgcc 1500
aagcctgtca ccgtagccgt gaagatgctg aaagatgatg ccactgacaa ggacctgtca 1560
gacctggtgt ctgagatgga gatgatgaag atgattggga aacacaagaa cattatcaac 1620
ctgctgggcg cctgcacgca gggcgggccc ctgtacgtgc tggtggagta cgcggccaag 1680
ggcaacctga gggagtttct gcgggcgcgg cggcccccgg gcctggacta ctccttcgac 1740
acctgcaagc cgcctgagga gcagctcacc ttcaaggacc tggtgtcctg tgcctaccag 1800
gtggcccgag gcatggagta cctcgcctcc cagaagtgca tccacaggga cctggctgct 1860
cgaaatgtgc tggtgaccga ggacaacgtg atgaagatcg cagacttcgg gctggcccgc 1920
gacgtgcaca accttgacta ctacaagaag acaaccaacg gccggctgcc cgtgaagtgg 1980
atggcgcctg aggccctgtt tgaccgagtc tacacccacc agagtgacgt ctggtccttt 2040
ggggtcctgc tctgggagat cttcacgctg gggggctctc cgtaccccgg catccctgtg 2100
gaggagctct tcaagctgct gaaggagggt caccggatgg acaagccggc caactgcaca 2160
cacgacctgt acatgatcat gcgggagtgc tggcatgctg cgccctccca gaggcccacc 2220
ttcaagcagc tggtggagga cctggaccgt gtcctcactg tgacgtccac cgacgagtac 2280
ctggacctgt cagcgccctt cgagcagtac tcccccggcg gccaggacac cccgagctcc 2340
agctcctcag gggatgactc cgtgtttgcc cacgacctgc tgcccccggc cccacccagc 2400
agtgggggct cgcggacgtg a 2421
<210> 137
<400> 137
000
<210> 138
<211> 806
<212> PRT
<213> Macaca fascicularis
<400> 138
Met Gly Ala Pro Ala Cys Ala Leu Ala Leu Cys Val Ala Val Ala Ile
1 5 10 15
Val Ala Gly Ala Ser Ser Glu Ser Leu Gly Thr Glu Gln Arg Val Val
20 25 30
Gly Arg Val Ala Glu Val Ser Gly Pro Glu Pro Ser Gln Gln Glu Gln
35 40 45
Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser Cys Pro Pro Pro
50 55 60
Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val Lys Asp Gly Ala Gly
65 70 75 80
Leu Val Pro Ser Glu Arg Val Leu Val Gly Pro Gln Arg Leu Gln Val
85 90 95
Leu Asn Ala Ser His Glu Asp Ser Gly Ala Tyr Ser Cys Arg Gln Arg
100 105 110
Leu Thr Gln Leu Val Leu Cys His Phe Ser Val Arg Val Thr Asp Ala
115 120 125
Pro Ser Ser Gly Asp Asp Glu Asp Gly Glu Asp Glu Ala Glu Asp Thr
130 135 140
Gly Val Asp Thr Gly Ala Pro Tyr Trp Thr Arg Pro Glu Arg Met Asp
145 150 155 160
Lys Lys Leu Leu Ala Val Pro Ala Ala Asn Thr Val Arg Phe Arg Cys
165 170 175
Pro Ala Ala Gly Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn Gly
180 185 190
Lys Glu Phe Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg His
195 200 205
Gln Gln Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly
210 215 220
Asn Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr
225 230 235 240
Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu Gln
245 250 255
Ala Gly Leu Pro Ala Asn Gln Thr Ala Val Leu Gly Ser Asp Val Glu
260 265 270
Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp Leu
275 280 285
Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro Asp Gly Thr Pro
290 295 300
Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn Thr Thr Asp Lys Glu
305 310 315 320
Leu Glu Val Leu Ser Leu His Asn Val Thr Phe Glu Asp Ala Gly Glu
325 330 335
Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Phe Ser His His Ser Ala
340 345 350
Trp Leu Val Val Leu Pro Ala Glu Glu Glu Leu Val Glu Ala Asp Glu
355 360 365
Ala Gly Ser Val Tyr Ala Gly Ile Leu Ser Tyr Gly Val Gly Phe Phe
370 375 380
Leu Phe Ile Leu Val Val Ala Ala Val Thr Leu Cys Arg Leu Arg Ser
385 390 395 400
Thr Pro Lys Lys Gly Leu Gly Ser Pro Thr Val His Lys Ile Ser Arg
405 410 415
Phe Pro Leu Lys Arg Gln Val Ser Leu Glu Ser Asn Ala Ser Met Ser
420 425 430
Ser Asn Thr Pro Leu Val Arg Ile Ala Arg Leu Ser Ser Gly Glu Gly
435 440 445
Pro Thr Leu Ala Asn Val Ser Glu Leu Glu Leu Pro Ala Asp Pro Lys
450 455 460
Trp Glu Leu Ser Arg Ala Arg Leu Thr Leu Gly Lys Pro Leu Gly Glu
465 470 475 480
Gly Cys Phe Gly Gln Val Val Met Ala Glu Ala Ile Gly Ile Asp Lys
485 490 495
Asp Arg Ala Ala Lys Pro Val Thr Val Ala Val Lys Met Leu Lys Asp
500 505 510
Asp Ala Thr Asp Lys Asp Leu Ser Asp Leu Val Ser Glu Met Glu Met
515 520 525
Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn Leu Leu Gly Ala
530 535 540
Cys Thr Gln Gly Gly Pro Leu Tyr Val Leu Val Glu Tyr Ala Ala Lys
545 550 555 560
Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg Arg Pro Pro Gly Leu Asp
565 570 575
Tyr Ser Phe Asp Thr Cys Lys Pro Pro Glu Glu Gln Leu Thr Phe Lys
580 585 590
Asp Leu Val Ser Cys Ala Tyr Gln Val Ala Arg Gly Met Glu Tyr Leu
595 600 605
Ala Ser Gln Lys Cys Ile His Arg Asp Leu Ala Ala Arg Asn Val Leu
610 615 620
Val Thr Glu Asp Asn Val Met Lys Ile Ala Asp Phe Gly Leu Ala Arg
625 630 635 640
Asp Val His Asn Leu Asp Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu
645 650 655
Pro Val Lys Trp Met Ala Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr
660 665 670
His Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Phe
675 680 685
Thr Leu Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe
690 695 700
Lys Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro Ala Asn Cys Thr
705 710 715 720
His Asp Leu Tyr Met Ile Met Arg Glu Cys Trp His Ala Ala Pro Ser
725 730 735
Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu Asp Arg Val Leu
740 745 750
Thr Val Thr Ser Thr Asp Glu Tyr Leu Asp Leu Ser Ala Pro Phe Glu
755 760 765
Gln Tyr Ser Pro Gly Gly Gln Asp Thr Pro Ser Ser Ser Ser Ser Gly
770 775 780
Asp Asp Ser Val Phe Ala His Asp Leu Leu Pro Pro Ala Pro Pro Ser
785 790 795 800
Ser Gly Gly Ser Arg Thr
805
<210> 139
<211> 806
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 139
Met Gly Ala Pro Ala Cys Ala Leu Ala Leu Cys Val Ala Val Ala Ile
1 5 10 15
Val Ala Gly Ala Ser Ser Glu Ser Leu Gly Thr Glu Gln Arg Val Val
20 25 30
Gly Arg Val Ala Glu Val Ser Gly Pro Glu Pro Ser Gln Gln Glu Gln
35 40 45
Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser Cys Pro Pro Pro
50 55 60
Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val Lys Asp Gly Ala Gly
65 70 75 80
Leu Val Pro Ser Glu Arg Val Leu Val Gly Pro Gln Arg Leu Gln Val
85 90 95
Leu Asn Ala Ser His Glu Asp Ser Gly Ala Tyr Ser Cys Arg Gln Arg
100 105 110
Leu Thr Gln Leu Val Leu Cys His Phe Ser Val Arg Val Thr Asp Ala
115 120 125
Pro Ser Ser Gly Asp Asp Glu Asp Gly Glu Asp Glu Ala Glu Asp Thr
130 135 140
Gly Val Asp Thr Gly Ala Pro Tyr Trp Thr Arg Pro Glu Arg Met Asp
145 150 155 160
Lys Lys Leu Leu Ala Val Pro Ala Ala Asn Thr Val Arg Phe Arg Cys
165 170 175
Pro Ala Ala Gly Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn Gly
180 185 190
Lys Glu Phe Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg His
195 200 205
Gln Gln Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly
210 215 220
Asn Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr
225 230 235 240
Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu Gln
245 250 255
Ala Gly Leu Pro Ala Asn Gln Thr Ala Val Leu Gly Ser Asp Val Glu
260 265 270
Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp Leu
275 280 285
Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro Asp Gly Thr Pro
290 295 300
Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn Thr Thr Asp Lys Glu
305 310 315 320
Leu Glu Val Leu Ser Leu His Asn Val Thr Phe Glu Asp Ala Gly Glu
325 330 335
Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Phe Ser His His Ser Ala
340 345 350
Trp Leu Val Val Leu Pro Ala Glu Glu Glu Leu Val Glu Ala Asp Glu
355 360 365
Ala Gly Ser Val Tyr Ala Gly Ile Leu Ser Tyr Arg Val Gly Phe Phe
370 375 380
Leu Phe Ile Leu Val Val Ala Ala Val Thr Leu Cys Arg Leu Arg Ser
385 390 395 400
Thr Pro Lys Lys Gly Leu Gly Ser Pro Thr Val His Lys Ile Ser Arg
405 410 415
Phe Pro Leu Lys Arg Gln Val Ser Leu Glu Ser Asn Ala Ser Met Ser
420 425 430
Ser Asn Thr Pro Leu Val Arg Ile Ala Arg Leu Ser Ser Gly Glu Gly
435 440 445
Pro Thr Leu Ala Asn Val Ser Glu Leu Glu Leu Pro Ala Asp Pro Lys
450 455 460
Trp Glu Leu Ser Arg Ala Arg Leu Thr Leu Gly Lys Pro Leu Gly Glu
465 470 475 480
Gly Cys Phe Gly Gln Val Val Met Ala Glu Ala Ile Gly Ile Asp Lys
485 490 495
Asp Arg Ala Ala Lys Pro Val Thr Val Ala Val Lys Met Leu Lys Asp
500 505 510
Asp Ala Thr Asp Lys Asp Leu Ser Asp Leu Val Ser Glu Met Glu Met
515 520 525
Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn Leu Leu Gly Ala
530 535 540
Cys Thr Gln Gly Gly Pro Leu Tyr Val Leu Val Glu Tyr Ala Ala Lys
545 550 555 560
Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg Arg Pro Pro Gly Leu Asp
565 570 575
Tyr Ser Phe Asp Thr Cys Lys Pro Pro Glu Glu Gln Leu Thr Phe Lys
580 585 590
Asp Leu Val Ser Cys Ala Tyr Gln Val Ala Arg Gly Met Glu Tyr Leu
595 600 605
Ala Ser Gln Lys Cys Ile His Arg Asp Leu Ala Ala Arg Asn Val Leu
610 615 620
Val Thr Glu Asp Asn Val Met Lys Ile Ala Asp Phe Gly Leu Ala Arg
625 630 635 640
Asp Val His Asn Leu Asp Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu
645 650 655
Pro Val Lys Trp Met Ala Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr
660 665 670
His Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Phe
675 680 685
Thr Leu Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe
690 695 700
Lys Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro Ala Asn Cys Thr
705 710 715 720
His Asp Leu Tyr Met Ile Met Arg Glu Cys Trp His Ala Ala Pro Ser
725 730 735
Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu Asp Arg Val Leu
740 745 750
Thr Val Thr Ser Thr Asp Glu Tyr Leu Asp Leu Ser Ala Pro Phe Glu
755 760 765
Gln Tyr Ser Pro Gly Gly Gln Asp Thr Pro Ser Ser Ser Ser Ser Gly
770 775 780
Asp Asp Ser Val Phe Ala His Asp Leu Leu Pro Pro Ala Pro Pro Ser
785 790 795 800
Ser Gly Gly Ser Arg Thr
805
<210> 140
<211> 390
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 140
Gly Gly Leu Asn Asp Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu
1 5 10 15
His His His His His His Glu Asp Gln Val Asp Pro Arg Leu Ile Asp
20 25 30
Gly Lys Ile Gln Pro Glu Pro Glu Ser Leu Gly Thr Glu Gln Arg Val
35 40 45
Val Gly Arg Ala Ala Glu Val Pro Gly Pro Glu Pro Gly Gln Gln Glu
50 55 60
Gln Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser Cys Pro Pro
65 70 75 80
Pro Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val Lys Asp Gly Thr
85 90 95
Gly Leu Val Pro Ser Glu Arg Val Leu Val Gly Pro Gln Arg Leu Gln
100 105 110
Val Leu Asn Ala Ser His Glu Asp Ser Gly Ala Tyr Ser Cys Arg Gln
115 120 125
Arg Leu Thr Gln Arg Val Leu Cys His Phe Ser Val Arg Val Thr Asp
130 135 140
Ala Pro Ser Ser Gly Asp Asp Glu Asp Gly Glu Asp Glu Ala Glu Asp
145 150 155 160
Thr Gly Val Asp Thr Gly Ala Pro Tyr Trp Thr Arg Pro Glu Arg Met
165 170 175
Asp Lys Lys Leu Leu Ala Val Pro Ala Ala Asn Thr Val Arg Phe Arg
180 185 190
Cys Pro Ala Ala Gly Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn
195 200 205
Gly Arg Glu Phe Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg
210 215 220
His Gln Gln Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg
225 230 235 240
Gly Asn Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln
245 250 255
Thr Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu
260 265 270
Gln Ala Gly Leu Pro Ala Asn Gln Thr Ala Val Leu Gly Ser Asp Val
275 280 285
Glu Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile Gln Trp
290 295 300
Leu Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro Asp Gly Thr
305 310 315 320
Pro Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn Thr Thr Asp Lys
325 330 335
Glu Leu Glu Val Leu Ser Leu His Asn Val Thr Phe Glu Asp Ala Gly
340 345 350
Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Phe Ser His His Ser
355 360 365
Ala Trp Leu Val Val Leu Pro Ala Glu Glu Glu Leu Val Glu Ala Asp
370 375 380
Glu Ala Gly Ser Ala Ser
385 390
<210> 141
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 141
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 142
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 142
Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 143
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 143
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 144
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 144
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Lys Phe
20 25 30
Ile Ala Trp Tyr Gln His Lys Pro Gly Lys Gly Pro Arg Leu Leu Ile
35 40 45
His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser Asn Leu Glu Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp Asn Leu Leu Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 145
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 145
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 146
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 146
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Ile Asn Lys Phe
20 25 30
Ile Ala Trp Tyr Gln His Lys Pro Gly Lys Gly Pro Arg Leu Leu Ile
35 40 45
His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser Asn Leu Glu Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Phe Cys Leu Gln Tyr Asp Asn Leu Leu Trp
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 147
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 147
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 148
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 148
Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly
1 5 10 15
Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Thr Gly
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Tyr Ile Leu Thr Ile Arg Ser Val Gln Ala
65 70 75 80
Glu Asp Leu Ala Leu Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Leu
85 90 95
Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 149
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 149
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 150
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 150
Asn Ile Met Met Thr Gln Ser Pro Ser Ser Leu Ala Val Ser Ala Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Ser Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 151
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 151
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 152
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 152
Asn Ile Met Met Thr Gln Ser Pro Ser Ser Leu Ala Val Ser Ala Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Ser
65 70 75 80
Ile Ser Ser Val Gln Thr Glu Asp Leu Ala Val Tyr Tyr Cys His Gln
85 90 95
Tyr Leu Ser Ser Tyr Thr Phe Gly Gly Gly Thr Arg Leu Glu Met Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 153
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 153
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 154
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 154
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser
20 25 30
Asp Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Tyr Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
115 120 125
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
130 135 140
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
145 150 155 160
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
180 185 190
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
195 200 205
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 155
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 155
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 156
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 156
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
<210> 157
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (2)..(2)
<223> /替代="D"
<220>
<221> 变体
<222> (7)..(7)
<223> /替代="Y"
<220>
<221> SITE
<222> (1)..(8)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 157
Gly Tyr Thr Phe Thr Asp Phe Glu
1 5
<210> 158
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (7)..(7)
<223> /替代="S"
<220>
<221> SITE
<222> (1)..(8)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 158
Ile Asp Pro Glu Thr Gly Gly Thr
1 5
<210> 159
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (7)..(7)
<223> /替代="V"
<220>
<221> SITE
<222> (1)..(8)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 159
Ile Asn Pro Asn Asn Gly Gly Thr
1 5
<210> 160
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (2)..(2)
<223> /替代="E"
<220>
<221> SITE
<222> (1)..(8)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 160
Val Asp Pro Glu Thr Gly Gly Thr
1 5
<210> 161
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (3)..(3)
<223> /替代="N"
<220>
<221> 变体
<222> (5)..(5)
<223> /替代="E"
<220>
<221> 变体
<222> (8)..(8)
<223> /替代="P"
<220>
<221> 变体
<222> (9)..(9)
<223> /替代="R" or "Y"
<220>
<221> 变体
<222> (10)..(10)
<223> /替代="A"
<220>
<221> 变体
<222> (11)..(11)
<223> /替代="M"
<220>
<221> SITE
<222> (1)..(13)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 161
Thr Arg Thr Tyr Asp Gly Tyr Ser Gln Thr Phe Asp Tyr
1 5 10
<210> 162
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (3)..(3)
<223> /替代="V"
<220>
<221> 变体
<222> (7)..(7)
<223> /替代="D" or "S"
<220>
<221> 变体
<222> (9)..(9)
<223> /替代="N"
<220>
<221> SITE
<222> (1)..(12)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 162
Gln Ser Leu Leu Tyr Ser Asn Asn Gln Lys Asn Tyr
1 5 10
<210> 163
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (1)..(1)
<223> /替代="Y" or "F"
<220>
<221> SITE
<222> (1)..(3)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 163
Trp Ala Ser
1
<210> 164
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 164
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 165
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 165
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 166
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 166
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 167
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 167
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 168
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 168
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 169
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 169
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 170
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 170
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 171
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 171
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 172
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 172
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser
210 215 220
<210> 173
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 173
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215 220
<210> 174
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 174
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215 220
<210> 175
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 175
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215 220
<210> 176
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 176
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215
<210> 177
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 177
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215 220
<210> 178
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 178
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215 220
<210> 179
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 179
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215 220
<210> 180
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 180
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215 220
<210> 181
<211> 221
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 181
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys
210 215 220
<210> 182
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 182
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
<210> 183
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 183
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215
<210> 184
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 184
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215
<210> 185
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 185
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215
<210> 186
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 186
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
<210> 187
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 187
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
<210> 188
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 188
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
<210> 189
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 189
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
<210> 190
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 190
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
<210> 191
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 191
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 192
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 192
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 193
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 193
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 194
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 194
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 195
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 195
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 196
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 196
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 197
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 197
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 198
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 198
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 199
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 199
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu
210 215
<210> 200
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 200
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 201
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 201
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 202
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 202
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 203
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 203
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 204
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 204
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 205
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 205
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 206
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 206
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 207
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 207
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 208
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 208
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val
210 215
<210> 209
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 209
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys
210 215
<210> 210
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 210
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys
210 215
<210> 211
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 211
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys
210 215
<210> 212
<211> 215
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 212
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys
210 215
<210> 213
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 213
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys
210 215
<210> 214
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 214
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys
210 215
<210> 215
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 215
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys
210 215
<210> 216
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 216
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys
210 215
<210> 217
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 217
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys
210 215
<210> 218
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 218
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys
210 215
<210> 219
<211> 215
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 219
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys
210 215
<210> 220
<211> 215
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 220
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys
210 215
<210> 221
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 221
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys
210
<210> 222
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 222
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys
210 215
<210> 223
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 223
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys
210 215
<210> 224
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 224
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys
210 215
<210> 225
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 225
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys
210 215
<210> 226
<211> 216
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 226
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys
210 215
<210> 227
<211> 230
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 227
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro
225 230
<210> 228
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 228
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro
225
<210> 229
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 229
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro
225
<210> 230
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 230
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
His Thr Cys Pro
225
<210> 231
<211> 230
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 231
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro
225 230
<210> 232
<211> 230
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 232
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro
225 230
<210> 233
<211> 230
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 233
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro
225 230
<210> 234
<211> 230
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 234
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro
225 230
<210> 235
<211> 230
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 235
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro
225 230
<210> 236
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 236
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys
225
<210> 237
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 237
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys
225
<210> 238
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 238
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys
225
<210> 239
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 239
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
His Thr Cys
225
<210> 240
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 240
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys
225
<210> 241
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 241
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys
225
<210> 242
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 242
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys
225
<210> 243
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 243
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys
225
<210> 244
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 244
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys
225
<210> 245
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 245
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr
225
<210> 246
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 246
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr
225
<210> 247
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 247
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr
225
<210> 248
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 248
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
His Thr
225
<210> 249
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 249
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr
225
<210> 250
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 250
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr
225
<210> 251
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 251
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr
225
<210> 252
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 252
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr
225
<210> 253
<211> 228
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 253
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr
225
<210> 254
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 254
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His
225
<210> 255
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 255
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His
225
<210> 256
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 256
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His
225
<210> 257
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 257
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
His
225
<210> 258
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 258
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His
225
<210> 259
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 259
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His
225
<210> 260
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 260
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His
225
<210> 261
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 261
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His
225
<210> 262
<211> 227
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 262
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His
225
<210> 263
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 263
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr
225
<210> 264
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 264
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr
225
<210> 265
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 265
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr
225
<210> 266
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 266
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr
210 215 220
<210> 267
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 267
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr
225
<210> 268
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 268
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr
225
<210> 269
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 269
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr
225
<210> 270
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 270
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr
225
<210> 271
<211> 226
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 271
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr
225
<210> 272
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 272
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys
225
<210> 273
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 273
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
<210> 274
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 274
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
<210> 275
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 275
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
<210> 276
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 276
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys
225
<210> 277
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 277
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys
225
<210> 278
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 278
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys
225
<210> 279
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 279
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys
225
<210> 280
<211> 225
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 280
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys
225
<210> 281
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 281
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 282
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 282
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Arg Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ala Met Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 283
<211> 223
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 283
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Gln Trp Ile
35 40 45
Gly Tyr Ile Asn Pro Asn Asn Gly Gly Thr Asn Tyr Asn Gln Asn Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asn Lys Ser Ser Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Arg Asp Tyr Asp Gly Ser Met Asp Phe Trp Gly Gln Gly
100 105 110
Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 284
<211> 222
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 284
Glu Val Gln Leu Gln Gln Ser Gly Pro Asp Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Val Thr Asp Tyr
20 25 30
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asn Pro Asn Asn Gly Val Thr Thr Tyr Asn Gln Lys Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Glu Asp Phe Asp Gly Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Thr Leu Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 285
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 285
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Ser Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Gly Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 286
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 286
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Ser Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Ile Leu Thr Ala Val Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gly Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 287
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 287
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 288
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 288
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 289
<211> 224
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 289
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Tyr Ile
35 40 45
Gly Asp Val Asp Pro Glu Thr Gly Gly Thr Ala Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr Ala Tyr
65 70 75 80
Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr Tyr Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
<210> 290
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (6)..(6)
<223> /替代="S"
<220>
<221> SITE
<222> (1)..(8)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 290
His Gln Tyr Leu Ser Pro Tyr Thr
1 5
<210> 291
<211> 449
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 291
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Ala Pro Ser Val
115 120 125
Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr
130 135 140
Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr
145 150 155 160
Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser
180 185 190
Ser Thr Trp Pro Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala
195 200 205
Ser Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Pro Thr Ile
210 215 220
Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Pro Val Ala Gly Pro
225 230 235 240
Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser
245 250 255
Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp
260 265 270
Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr
275 280 285
Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val
290 295 300
Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu
305 310 315 320
Phe Lys Cys Lys Val Asn Asn Lys Gly Leu Pro Ser Ser Ile Glu Arg
325 330 335
Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val
340 345 350
Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr
355 360 365
Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr
370 375 380
Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys
405 410 415
Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu
420 425 430
Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly
435 440 445
Lys
<210> 292
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 292
Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu
115 120 125
Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe
130 135 140
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg
145 150 155 160
Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu
180 185 190
Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser
195 200 205
Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 293
<211> 217
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 293
Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Ala
1 5 10 15
Ser Val Thr Leu Ser Cys Lys Ala Ser Gly Asp Thr Phe Thr Asp Phe
20 25 30
Glu Ile His Trp Val Lys Gln Thr Pro Val His Gly Leu Glu Trp Ile
35 40 45
Gly Asp Ile Asp Pro Glu Thr Gly Gly Thr Ala Tyr Asn Gln Lys Phe
50 55 60
Arg Gly Arg Ala Met Leu Thr Ala Asp Arg Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Ala Pro Ser Val
115 120 125
Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr
130 135 140
Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr
145 150 155 160
Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser
180 185 190
Ser Thr Trp Pro Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala
195 200 205
Ser Ser Thr Lys Val Asp Lys Lys Ile
210 215
<210> 294
<211> 219
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 294
Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly
1 5 10 15
Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser
20 25 30
Asn Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln
35 40 45
Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val
50 55 60
Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
65 70 75 80
Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln
85 90 95
Tyr Tyr Ser Tyr Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu
115 120 125
Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe
130 135 140
Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg
145 150 155 160
Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser
165 170 175
Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu
180 185 190
Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser
195 200 205
Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys
210 215
<210> 295
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 295
Gly Asp Thr Phe Thr Asp Tyr Glu
1 5
<210> 296
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 296
Gly Tyr Thr Phe Thr Asp Phe Glu
1 5
<210> 297
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 297
Val Asp Pro Glu Thr Gly Gly Thr
1 5
<210> 298
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 298
Ile Asp Pro Glu Thr Gly Ser Thr
1 5
<210> 299
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 299
Val Glu Pro Glu Thr Gly Gly Thr
1 5
<210> 300
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 300
Thr Arg Thr Tyr Glu Gly Tyr Pro Tyr Ala Met Asp Tyr
1 5 10
<210> 301
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 301
Thr Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Phe Asp Tyr
1 5 10
<210> 302
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 302
Gln Ser Val Leu Tyr Ser Asn Asn Asn Lys Asn Tyr
1 5 10
<210> 303
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 303
Tyr Ala Ser
1
<210> 304
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 304
Phe Ala Ser
1
<210> 305
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 305
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Phe Asp Tyr
1 5 10
<210> 306
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 306
Gln Ser Val Leu Tyr Ser Asp Asn Gln Lys Asn Tyr
1 5 10
<210> 307
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 307
Thr Arg Asn Tyr Asp Gly Tyr Ser Arg Thr Phe Asp Tyr
1 5 10
<210> 308
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (11)..(11)
<223> /替代="F"
<220>
<221> SITE
<222> (1)..(13)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 308
Thr Arg Asn Tyr Asp Gly Tyr Ser Gln Thr Met Asp Tyr
1 5 10
<210> 309
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<220>
<221> 变体
<222> (7)..(7)
<223> /替代="D"
<220>
<221> SITE
<222> (1)..(12)
<223> /注释="序列中给出的变体残基关于变体位置的注解中的那些没有优先性"
<400> 309
Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Asn Tyr
1 5 10
<210> 310
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 310
Ala Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Tyr
1 5 10
<210> 311
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 311
Ala Arg Thr Tyr Asp Gly Tyr Pro Tyr Ala Met Asp Val
1 5 10
<210> 312
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 312
Ile Asp Pro Glu Ser Gly Gly Thr
1 5
<210> 313
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 313
Ile Glu Pro Glu Ser Gly Gly Thr
1 5
<210> 314
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 314
His Gln Tyr Leu Ser Pro Tyr Thr
1 5
<210> 315
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 315
Gln Ser Val Leu Tyr Ser Asn Asn Gln Lys Asn Tyr
1 5 10
<210> 316
<211> 3
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 316
Trp Gly Ser
1
<210> 317
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 317
Gln Ser Leu Leu His Ser Asn Asn Gln Lys Asn Tyr
1 5 10
<210> 318
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 318
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Arg Gln
65 70 75 80
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Asn Gln
130 135 140
Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 319
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 319
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Arg Gln
65 70 75 80
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Asn Gln
130 135 140
Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 320
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 320
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Arg Gln
65 70 75 80
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Asn Gln
130 135 140
Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 321
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 321
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Arg Gln
65 70 75 80
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Ala Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Asn Gln
130 135 140
Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Ser Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 322
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 322
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Arg Gln
65 70 75 80
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Gly Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Asn Gln
130 135 140
Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 323
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 323
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Arg Gln
65 70 75 80
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Gly Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Asn Gln
130 135 140
Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 324
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 324
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Arg Gln
65 70 75 80
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Gly Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Asn Gln
130 135 140
Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 325
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 325
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Arg Gln
65 70 75 80
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Gly Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Asn Gln
130 135 140
Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Arg Ser Thr Ser Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 326
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 326
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Gln Gln
65 70 75 80
Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Asp Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Ala Glu
130 135 140
Lys Phe Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr
145 150 155 160
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 327
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 327
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Gln Gln
65 70 75 80
Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Asp Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Ala Glu
130 135 140
Lys Phe Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr
145 150 155 160
Ala Tyr Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 328
<211> 238
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (26)..(74)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (26)..(74)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (92)..(140)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (92)..(140)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (179)..(227)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (179)..(227)
<223> /注释="该序列可包含3-49个残基"
<400> 328
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Leu Ser Cys Lys Ala Ser Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ile His Trp Val Gln Gln
65 70 75 80
Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly Asp Xaa Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Ala Tyr Ala Glu
130 135 140
Lys Phe Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Asp Thr
145 150 155 160
Ala Tyr Leu Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
165 170 175
Tyr Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Xaa Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 329
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 329
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 330
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 330
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 331
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 331
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 332
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 332
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 333
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 333
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 334
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 334
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 335
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 335
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 336
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 336
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 337
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 337
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
225 230 235
<210> 338
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 338
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
225 230 235
<210> 339
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<220>
<221> MOD_RES
<222> (27)..(75)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (27)..(75)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (93)..(141)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (93)..(141)
<223> /注释="该序列可包含3-49个残基"
<220>
<221> MOD_RES
<222> (178)..(226)
<223> 任何天然存在的氨基酸
<220>
<221> SITE
<222> (178)..(226)
<223> /注释="该序列可包含3-49个残基"
<400> 339
Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly
1 5 10 15
Glu Arg Val Thr Ile Asn Cys Lys Ser Ser Xaa Xaa Xaa Xaa Xaa Xaa
20 25 30
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
35 40 45
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
50 55 60
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Ala Trp Tyr Gln
65 70 75 80
Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Xaa Xaa Xaa Xaa
85 90 95
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
100 105 110
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
115 120 125
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Thr Arg Glu
130 135 140
Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
145 150 155 160
Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Val Ala Val Tyr Tyr
165 170 175
Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
180 185 190
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
195 200 205
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
210 215 220
Xaa Xaa Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
225 230 235
<210> 340
<211> 17
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 340
Ile His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Gly
1 5 10 15
Asp
<210> 341
<211> 38
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成多肽"
<400> 341
Ala Tyr Ala Glu Lys Phe Gln Gly Arg Ala Thr Leu Thr Ala Asp Arg
1 5 10 15
Ser Thr Asp Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp
20 25 30
Thr Ala Val Tyr Tyr Cys
35
<210> 342
<211> 11
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 342
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 343
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 343
Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr
1 5 10
<210> 344
<211> 12
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述：合成肽"
<400> 344
Gln Gly Ile Ser Tyr Ser Asn Asn Gln Lys Asn Tyr
1 5 10
Claims (81)
1.一种与成纤维细胞生长因子受体3(FGFR3)特异性结合的抗原结合蛋白或其抗原结合片段，其包含抗体重链可变(VH)结构域和抗体轻链可变(VL)结构域，其中：
(a)所述VH结构域包含
含有氨基酸序列GX1TFTDX2E(SEQ ID NO:157)的CDR-H1序列，其中X1是Y或D并且X2是F或Y；
含有氨基酸序列IDPETGX3T(SEQ ID NO:158)的CDR-H2序列，其中X3是G或S；或含有氨基酸序列INPNNGX4T(SEQ ID NO:159)的CDR-H2序列，其中X4是G或V；或含有氨基酸序列VX5PETGGT(SEQ ID NO:160)的CDR-H2序列，其中X5是D或E；
含有氨基酸序列TRX6YX7GYX8X9X10X11DY(SEQ ID NO:161)的CDR-H3序列，其中X6是T或N，X7是D或E，X8是S或P，X9是Q、R或Y，X10是T或A，X11是F或M；以及
所述VL结构域包含
含有氨基酸序列QSX12LYSX13NX14KNY(SEQ ID NO:162)的CDR-L1序列，其中X12是L或V，X13是N、D或S，并且X14是Q或N；
含有氨基酸序列X15AS(SEQ ID NO:163)的CDR-L2序列，其中X15是W、Y或F；
含有氨基酸序列QQYYSYRT(SEQ ID NO:75)、LQYDNLLWT(SEQ IDNO:81)或HQYLSX16YT(SEQ ID NO:290)的CDR-L3序列，其中X16是P或S；
(b)所述VH结构域包含
含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；
含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；
含有氨基酸序列ARERDYDGAMDY(SEQ ID NO:78)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；
含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；
含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；(c)所述VH结构域包含
含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；
含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGSMDF(SEQ ID NO:84)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；
含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；
含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；(d)所述VH结构域包含
含有氨基酸序列GYTVTDYY(SEQ ID NO:88)的CDR-H1序列；
含有氨基酸序列INPNNGVT(SEQ ID NO:89)的CDR-H2序列；
含有氨基酸序列AREEDFDGFDY(SEQ ID NO:90)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QDVSTG(SEQ ID NO:91)的CDR-L1序列；
含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列QQHYSTPLT(SEQ ID NO:93)的CDR-L3序列；
(e)所述VH结构域包含
含有氨基酸序列GSTFSDFE(SEQ ID NO:94)的CDR-H1序列；
含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；
含有氨基酸序列TRNYDGYSQTX17DY(SEQ ID NO:308)的CDR-H3序列，其中X17是M或F；以及
所述VL结构域包含
含有氨基酸序列QSVLYSX18NQKNY(SEQ ID NO:309)的CDR-L1序列，其中X18是S或D；
含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列；或
(f)所述VH结构域包含
含有氨基酸序列GSTFTDFE(SEQ ID NO:100)的CDR-H1序列；
含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；
含有氨基酸序列TRNYDGYSQTX17DY(SEQ ID NO:308)的CDR-H3序列，其中X17是M或F；以及
所述VL结构域包含
含有氨基酸序列QSVLYSX18NQKNY(SEQ ID NO:309)的CDR-L1序列，
其中X18是S或D；
含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列。
2.根据权利要求1所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含
含有氨基酸序列GDTFTDFE(SEQ ID NO:70)、GDTFTDYE(SEQ IDNO:295)或GYTFTDFE(SEQID NO:296)的CDR-H1序列；
含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)、VDPETGGT(SEQ ID NO:297)、IDPETGST(SEQ ID NO:298)或VEPETGGT(SEQID NO:298)的CDR-H2序列；
含有氨基酸序列TRTYDGYPYAMDY(SEQ ID NO:72)、TRTYEGYPYAMDY(SEQ ID NO:300)或TRTYDGYPYAFDY(SEQ IDNO:301)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QSLLYSNNQKNY(SEQ ID NO:73)、QSVLYSNNNKNY(SEQ ID NO:302)或QSVLYSDNQKNY(SEQ IDNO:306)的CDR-L1序列；
含有氨基酸序列WAS(SEQ ID NO:74、92、98、104)、YAS(SEQ IDNO:303)或FAS(SEQ IDNO:304)的CDR-L2序列；
含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列；
(b)所述VH结构域包含
含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；
含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；
含有氨基酸序列ARERDYDGAMDY(SEQ ID NO:78)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；
含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；
含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；(c)所述VH结构域包含
含有氨基酸序列GYTFTDYN(SEQ ID NO:76和80)的CDR-H1序列；
含有氨基酸序列INPNNGGT(SEQ ID NO:77和83)的CDR-H2序列；含有氨基酸序列ARERDYDGSMDF(SEQ ID NO:84)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QDINKF(SEQ ID NO:79和85)的CDR-L1序列；
含有氨基酸序列YTS(SEQ ID NO:80和86)的CDR-L2序列；
含有氨基酸序列LQYDNLLWT(SEQ ID NO:81和87)的CDR-L3序列；(d)所述VH结构域包含
含有氨基酸序列GYTVTDYY(SEQ ID NO:88)的CDR-H1序列；
含有氨基酸序列INPNNGVT(SEQ ID NO:89)的CDR-H2序列；
含有氨基酸序列AREEDFDGFDY(SEQ ID NO:90)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QDVSTG(SEQ ID NO:91)的CDR-L1序列；
含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列QQHYSTPLT(SEQ ID NO:93)的CDR-L3序列；
(e)所述VH结构域包含
含有氨基酸序列GSTFSDFE(SEQ ID NO:94)的CDR-H1序列；
含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；
含有氨基酸序列TRNYDGYSQTMDY(SEQ ID NO:96)或TRNYDGYSQTFDY(SEQ ID NO:305)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QSVLYSSNQKNY(SEQ ID NO:97和103)或QSVLYSDNQKNY(SEQ ID NO:306)的CDR-L1序列；
含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；
含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列；或
(f)所述VH结构域包含
含有氨基酸序列GSTFTDFE(SEQ ID NO:100)的CDR-H1序列；
含有氨基酸序列IDPETGGT(SEQ ID NO:71、95和101)的CDR-H2序列；
含有氨基酸序列TRNYDGYSRTMDY(SEQ ID NO:102)或TRNYDGYSRTFDY(SEQ ID NO:307)的CDR-H3序列；以及
所述VL结构域包含
含有氨基酸序列QSVLYSSNQKNY(SEQ ID NO:97和103)或QSVLYSDNQKNY(SEQ ID NO:306)的CDR-L1序列；
含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列；含有氨基酸序列HQYLSSYT(SEQ ID NO:99和105)的CDR-L3序列。
3.根据权利要求1或2所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含选自以下的氨基酸序列：
SEQ ID NO:6、SEQ ID NO:18、SEQ ID NO:57、SEQ ID NO:58、SEQID NO:106、SEQ IDNO:107、SEQ ID NO:108、SEQ ID NO:10、SEQID NO:110、SEQ ID NO:115、SEQ ID NO:116、SEQ ID NO:117、SEQID NO:118、SEQ ID NO:119、SEQ ID NO:120、SEQ ID NO:121和SEQIDNO:122；以及
所述VL结构域包含选自以下的氨基酸序列：
SEQ ID NO:7、SEQ ID NO:19、SEQ ID NO:60、SEQ ID NO:61、SEQID NO:112、SEQ IDNO:113、SEQ ID NO:114、SEQ ID NO:123、SEQID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ ID NO:127、SEQID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ ID NO:131和SEQIDNO:132；
(b)所述VH结构域包含氨基酸序列SEQ ID NO:8；以及
所述VL结构域包含氨基酸序列SEQ ID NO:9；
(c)所述VH结构域包含氨基酸序列SEQ ID NO:10；以及
所述VL结构域包含氨基酸序列SEQ ID NO:11；
(d)所述VH结构域包含氨基酸序列SEQ ID NO:12；以及
所述VL结构域包含氨基酸序列SEQ ID NO:13；
(e)所述VH结构域包含选自以下的氨基酸序列：
SEQ ID NO:14、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22和SEQID NO:23；以及
所述VL结构域包含选自以下的氨基酸序列：
SEQ ID NO:15、SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26和SEQID NO:27；
(f)所述VH结构域包含选自以下的氨基酸序列：
SEQ ID NO:16、SEQ ID NO:28、SEQ ID NO:29、SEQ ID NO:30和SEQID NO:31；
所述VL结构域包含选自以下的氨基酸序列：
SEQ ID NO:17、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34和SEQID NO:35。
4.根据权利要求1-3中任一项中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗体重链包含氨基酸序列SEQ ID NO:63或65，并且所述抗体轻链包含氨基酸序列SEQID NO:67或69。
5.根据权利要求3所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域与氨基酸序列SEQ ID NO:6、SEQ ID NO:8、SEQ ID NO:10、SEQID NO:12、SEQ ID NO:14、SEQ IDNO:16、SEQ ID NO:18、SEQ IDNO:20、SEQ ID NO:21、SEQ ID NO:22、SEQ ID NO:23、SEQ IDNO:28、SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:56、SEQ ID NO:57、SEQ IDNO:58、SEQ ID NO:63、SEQ ID NO:65、SEQID NO:106、SEQ ID NO:107、SEQ ID NO:108、SEQID NO:109、SEQID NO:110、SEQ ID NO:111、SEQ ID NO:115、SEQ ID NO:116、SEQID NO:117、SEQ ID NO:118、SEQ ID NO:119、SEQ ID NO:120、SEQID NO:121或SEQ ID NO:122具有至少约90％同一性或至少约95％同一性，并且
其中所述VL结构域与氨基酸序列SEQ ID NO:7、SEQ ID NO:9、SEQ IDNO:11、SEQ IDNO:13、SEQ ID NO:15、SEQ ID NO:17、SEQ ID NO:19、SEQ ID NO:24、SEQ ID NO:25、SEQ IDNO:26、SEQ ID NO:27、SEQ ID NO:32、SEQ ID NO:33、SEQ ID NO:34、SEQ ID NO:35、SEQIDNO:59、SEQ ID NO:60、SEQ ID NO:61、SEQ ID NO:67、SEQ IDNO:69、SEQ ID NO:112、SEQ IDNO:113、SEQ ID NO:114、SEQ IDNO:123、SEQ ID NO:124、SEQ ID NO:125、SEQ ID NO:126、SEQ IDNO:127、SEQ ID NO:128、SEQ ID NO:129、SEQ ID NO:130、SEQ IDNO:131、SEQ IDNO:132具有至少约90％同一性或至少约95％同一性。
6.根据权利要求5所述的抗原结合蛋白或其片段，其包含与氨基酸序列SEQ ID NO:63或65具有至少约90％同一性或至少约95％同一性的抗体重链和与氨基酸序列SEQ ID NO:67或69具有至少约90％同一性或至少约95％同一性的抗体轻链。
7.根据权利要求1-5中任一项所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ ID NO:70)的CDR-H1序列、含有氨基酸序列IDPETGGT(SEQ ID NO:71)的CDR-H2序列、和含有氨基酸序列TRTYDGYPYAMDY(SEQ ID NO:72)的CDR-H3序列；以及
(b)所述VL结构域包含：含有氨基酸序列QSLLYSNNQKNY(SEQ IDNO:73)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:74)的CDR-L2序列、和含有氨基酸序列QQYYSYRT(SEQ IDNO:75)的CDR-L3序列。
8.根据权利要求7所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域包含氨基酸序列SEQ ID NO:6，并且所述VL结构域包含氨基酸序列SEQ ID NO:7。
9.根据权利要求1-5中任一项所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:76)的CDR-H1序列、含有氨基酸序列INPNNGGT(SEQ ID NO:77)的CDR-H2序列、和含有氨基酸序列ARERDYDGAMDY(SEQID NO:78)的CDR-H3序列；以及
(b)所述VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:79)的CDR-L1序列、含有氨基酸序列YTS(SEQ ID NO:80)的CDR-L2序列、和含有氨基酸序列LQYDNLLWT(SEQ ID NO:81)的CDR-L3序列。
10.根据权利要求9所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域包含氨基酸序列SEQ ID NO:8，并且所述VL结构域包含氨基酸序列SEQ ID NO:9。
11.根据权利要求1-5中任一项所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含：含有氨基酸序列GYTFTDYN(SEQ ID NO:82)的CDR-H1序列、含有氨基酸序列INPNNGGT(SEQ ID NO:83)的CDR-H2序列、和含有氨基酸序列ARERDYDGSMDF(SEQID NO:84)的CDR-H3序列；以及
(b)所述VL结构域包含：含有氨基酸序列QDINKF(SEQ ID NO:85)的CDR-L1序列、含有氨基酸序列YTS(SEQ ID NO:86)的CDR-L2序列、和含有氨基酸序列LQYDNLLWT(SEQ ID NO:87)的CDR-L3序列。
12.根据权利要求11所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域包含氨基酸序列SEQ ID NO:10，并且所述VL结构域包含氨基酸序列SEQ ID NO:11。
13.根据权利要求1-5中任一项所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含：含有氨基酸序列GYTVTDYY(SEQ ID NO:88)的CDR-H1序列、含有氨基酸序列INPNNGVT(SEQ ID NO:89)的CDR-H2序列、和含有氨基酸序列AREEDFDGFDY(SEQID NO:90)的CDR-H3序列；以及
(b)所述VL结构域包含：含有氨基酸序列QDVSTG(SEQ ID NO:91)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:92)的CDR-L2序列、和含有氨基酸序列QQHYSTPLT(SEQ ID NO:93)的CDR-L3序列。
14.根据权利要求13所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域包含氨基酸序列SEQ ID NO:12，并且所述VL结构域包含氨基酸序列SEQ ID NO:13。
15.根据权利要求1-5中任一项所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含：含有氨基酸序列GSTFSDFE(SEQ ID NO:94)的CDR-H1序列、含有氨基酸序列IDPETGGT(SEQ ID NO:95)的CDR-H2序列、和含有氨基酸序列TRNYDGYSQTMDY(SEQ ID NO:96)的CDR-H3序列；以及
(b)所述VL结构域包含：含有氨基酸序列QSVLYSSNQKNY(SEQ IDNO:97)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:98)的CDR-L2序列、和含有氨基酸序列HQYLSSYT(SEQ IDNO:99)的CDR-L3序列。
16.根据权利要求15所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域包含氨基酸序列SEQ ID NO:14，并且所述VL结构域包含氨基酸序列SEQ ID NO:15。
17.根据权利要求1-5中任一项所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含：含有氨基酸序列GSTFTDFE(SEQ ID NO:100)的CDR-H1序列、含有氨基酸序列IDPETGGT(SEQ ID NO:101)的CDR-H2序列、和含有氨基酸序列TRNYDGYSRTMDY(SEQ ID NO:102)的CDR-H3序列；以及
(b)所述VL结构域包含：含有氨基酸序列QSVLYSSNQKNY(SEQ IDNO:103)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:104)的CDR-L2序列、和含有氨基酸序列HQYLSSYT(SEQ IDNO:105)的CDR-L3序列。
18.根据权利要求17所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域包含氨基酸序列SEQ ID NO:16，并且所述VL结构域包含氨基酸序列SEQ ID NO:17。
19.根据权利要求1-5中任一项所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ ID NO:70)的CDR-H1序列、含有氨基酸序列VDPETGGT(SEQ ID NO:297)的CDR-H2序列、和含有氨基酸序列TRTYDGYPYAFDY(SEQ ID NO:301)的CDR-H3序列；以及
(b)所述VL结构域包含：含有氨基酸序列QSVLYSNNNKNY(SEQ IDNO:302)的CDR-L1序列、含有氨基酸序列WAS(SEQ ID NO:74、92、98和104)的CDR-L2序列、和含有氨基酸序列QQYYSYRT(SEQ ID NO:75)的CDR-L3序列。
20.根据权利要求19所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域包含氨基酸序列SEQ ID NO:57，并且所述VL结构域包含氨基酸序列SEQ ID NO:19或59。
21.根据权利要求19所述的抗原结合蛋白或其抗原结合片段，其中所述抗体重链包含氨基酸序列SEQ ID NO:63，并且所述抗体轻链包含氨基酸序列SEQ ID NO:67。
22.根据权利要求1-5中任一项所述的抗原结合蛋白或其抗原结合片段，其中：
(a)所述VH结构域包含：含有氨基酸序列GDTFTDFE(SEQ ID NO:70)的CDR-H1序列、含有氨基酸序列VDPETGGT(SEQ ID NO:297)的CDR-H2序列、和含有氨基酸序列TRTYDGYPYAFDY(SEQ ID NO:301)的CDR-H3序列；以及
(b)所述VL结构域包含：含有氨基酸序列QSVLYSDNQKNY(SEQ IDNO:306)的CDR-L1序列、含有氨基酸序列FAS(SEQ ID NO:304)的CDR-L2序列、和含有氨基酸序列QQYYSYRT(SEQ IDNO:75)的CDR-L3序列。
23.根据权利要求22所述的抗原结合蛋白或其抗原结合片段，其中所述VH结构域包含氨基酸序列SEQ ID NO:57，并且所述VL结构域包含氨基酸序列SEQ ID NO:61。
24.根据权利要求22所述的抗原结合蛋白或其抗原结合片段，其中所述抗体重链包含氨基酸序列SEQ ID NO:65，并且所述抗体轻链包含氨基酸序列SEQ ID NO:67。
25.根据权利要求1-24中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段结合包含氨基酸序列SEQID NO:133的人FGFR3多肽。
26.根据权利要求1-24中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合片段结合包含氨基酸序列SEQ IDNO:134的人FGFR3多肽。
27.根据权利要求1-26中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合片段结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至L163。
28.根据权利要求1-26中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合片段结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至N170。
29.根据权利要求1-26中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合片段结合人FGFR3多肽的区域，所述区域包含SEQ ID NO:133的氨基酸D143至D160和氨基酸G197至L213。
30.根据权利要求1-29中任一项所述的抗原结合蛋白或其抗原结合片段，其中所述抗原结合蛋白或其抗原结合结合片段是嵌合或人源化抗体或其抗原结合结合片段。
31.根据权利要求1-29中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段是人抗体或其抗原结合结合片段。
32.根据权利要求1-31中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段是单克隆抗体或其抗原结合结合片段。
33.根据权利要求1-32中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段包含一个或多个包含Fc区的全长抗体重链。
34.根据权利要求33所述的抗原结合蛋白或其抗原结合片段，其中所述Fc区是人IgG1Fc区。
35.根据权利要求1-32中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段包括抗体F(ab)、F(ab')2、Fab'-SH、Fv或scFv片段。
36.根据权利要求1-32中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段包括抗体F(ab)片段。
37.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体F(ab)片段包含SEQ ID NO:56、和SEQ ID NO:54的前约100个氨基酸。
38.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段包含重链，所述重链包含SEQ ID NO:57、和SEQ ID NO:54的前约100个氨基酸。
39.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段包含重链，所述重链包含SEQ ID NO:58、和SEQ ID NO:54的前约100个氨基酸。
40.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:141、164、173、182、191、200、209、218、227、236、245、254、263、272或281，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:142。
41.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:143、165、174、183、192、201、210、219、228、237、246、255、264、273或282，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:144。
42.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:145、166、175、184、193、202、211、220、229、238、247、256、265、274或283，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:146。
43.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:147、167、176、185、194、203、212、221、230、239、248、257、266、275或284，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:148。
44.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:149、168、177、186、195、204、213、222、231、240、249、258、267、276或285，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:150。
45.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:151、169、178、187、196、205、214、223、232、241、250、259、268、277或286，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:152。
46.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
47.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
48.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:153、170、179、188、197、206、215、224、233、242、251、260、269、278或287，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
49.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
50.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
51.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:155、171、180、189、198、207、216、225、234、243、252、261、270、279或288，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
52.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:67。
53.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:154。
54.根据权利要求36所述的抗原结合蛋白或其抗原结合片段，其中所述抗体
F(ab)片段重链包含氨基酸序列SEQ ID NO:156、172、181、190、199、208、217、226、235、244、253、262、271、280或289，并且所述抗体
F(ab)片段轻链包含氨基酸序列SEQ ID NO:69。
55.根据权利要求1-54中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段具有与小鼠和食蟹猴FGFR3的交叉反应性。
56.根据权利要求1-55中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合或其抗原结合结合片段蛋白不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
57.根据权利要求1-56中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段不与FGFR1、FGFR2和FGFR4中的每一种结合。
58.根据权利要求1-56中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段以100μM或更大的平衡解离常数(KD)与FGFR1、FGFR2和FGFR4中的每一种结合。
59.根据权利要求1-58中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段以10nM或更小的平衡解离常数(KD)结合人FGFR3。
60.根据权利要求1-59中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段以10-4或更大的解离速率(Kd)结合人FGFR3。
61.根据权利要求1-60中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段以5μg/ml或更小的IC50抑制配体诱导的FGFR3二聚化。
62.根据权利要求1-61中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合结合片段以5μg/ml或更小的IC50抑制FGFR3受体激活和下游信号传导。
63.根据权利要求1-62中任一项所述的抗原结合蛋白或其抗原结合片段，其中：所述抗原结合蛋白或其抗原结合片段抑制FGFR3G380R突变体的活性。
64.根据权利要求1-63中任一项所述的抗原结合蛋白或其抗原结合片段，其能够穿透骨生长板。
65.根据权利要求1-64中任一项所述的抗原结合蛋白或其抗原结合片段，其能够降低在骨生长板中FGFR3与其配体的结合。
66.一种药物组合物，其包含根据前述权利要求中任一项所述的抗原结合蛋白或其抗原结合片段以及药学上可接受的载体。
67.一种分离的核酸分子，其编码根据前述权利要求中任一项所述的抗原结合蛋白或其抗原结合片段。
68.一种表达载体，其包含根据权利要求67所述的核酸分子。
69.一种宿主细胞，其包含根据权利要求68所述的表达载体。
70.一种用于治疗受试者的FGFR3介导的疾病或障碍的方法，其包括向有需要的受试者施用根据前述权利要求中任一项所述的抗原结合蛋白或其抗原结合片段。
71.根据权利要求70所述的方法，其中所述FGFR3介导的疾病或障碍是软骨发育不全。
72.根据权利要求71所述的方法，其中所述软骨发育不全是FGFR3G380R+软骨发育不全。
73.根据权利要求70所述的方法，其中患有软骨发育不全的所述受试者包括选自以下的一种或多种症状：近端肢体缩短、短指、大头伴有显著前额额部隆起、面中部小伴有鼻梁扁平、脊柱后凸、脊柱前凸、内翻、外翻、耳部感染、睡眠呼吸暂停、和脑积水。
74.根据权利要求70所述的方法，其中所述FGFR3介导的疾病或障碍是癌症。
75.根据权利要求74所述的方法，其中所述癌症是膀胱癌黑色素瘤、尿路上皮癌和子宫内膜癌。
76.一种用于治疗受试者的软骨发育不全的方法，其包括向有需要的受试者施用与FGFR3特异性结合的抗原结合蛋白片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
77.一种用于抑制受试者的骨生长板中FGFR3活性和表达中的一者或两者的方法，其包括向受试者施用与FGFR3特异性结合的抗原结合蛋白片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
78.根据权利要求70-77中任一项所述的方法，其中所述受试者是儿童。
79.根据权利要求78所述的方法，其中所述儿童是婴儿。
80.根据权利要求79所述的方法，其中所述婴儿是新生儿。
81.一种用于预防或减轻受试者的软骨发育不全的一种或多种症状的方法，其包括向所述受试者施用与FGFR3特异性结合的抗原结合蛋白或其抗原结合蛋白片段，其中所述抗原结合蛋白片段不与FGFR1、FGFR2和FGFR4中的一种或多种结合。
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| BR112023002455A2 (pt) | 2023-03-28 |
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| IL300623A (en) | 2023-04-01 |
| AR123306A1 (es) | 2022-11-16 |
| KR20230052963A (ko) | 2023-04-20 |
| JP2023538098A (ja) | 2023-09-06 |
| AU2021327387A1 (en) | 2023-05-04 |
| CO2023001559A2 (es) | 2023-02-16 |
| MX2023002106A (es) | 2023-03-15 |
| TW202229343A (zh) | 2022-08-01 |
| CA3189470A1 (en) | 2022-02-24 |
| AU2021327387A9 (en) | 2023-07-06 |
| EP4200019A1 (en) | 2023-06-28 |
| US20220056142A1 (en) | 2022-02-24 |
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