CN113736762A - 一种α-L-鼠李糖苷酶突变体及其在制备普鲁宁中的应用 - Google Patents
一种α-L-鼠李糖苷酶突变体及其在制备普鲁宁中的应用 Download PDFInfo
- Publication number
- CN113736762A CN113736762A CN202111144381.7A CN202111144381A CN113736762A CN 113736762 A CN113736762 A CN 113736762A CN 202111144381 A CN202111144381 A CN 202111144381A CN 113736762 A CN113736762 A CN 113736762A
- Authority
- CN
- China
- Prior art keywords
- ser
- ala
- gly
- thr
- leu
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 108010044879 alpha-L-rhamnosidase Proteins 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims description 7
- 150000001413 amino acids Chemical class 0.000 claims abstract description 16
- 230000035772 mutation Effects 0.000 claims abstract description 13
- 108090000623 proteins and genes Proteins 0.000 claims description 11
- 239000002773 nucleotide Substances 0.000 claims description 4
- 125000003729 nucleotide group Chemical group 0.000 claims description 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 239000001606 7-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)chroman-4-one Substances 0.000 abstract description 23
- DFPMSGMNTNDNHN-ZPHOTFPESA-N naringin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](OC=2C=C3O[C@@H](CC(=O)C3=C(O)C=2)C=2C=CC(O)=CC=2)O[C@H](CO)[C@@H](O)[C@@H]1O DFPMSGMNTNDNHN-ZPHOTFPESA-N 0.000 abstract description 23
- 229930019673 naringin Natural products 0.000 abstract description 23
- 229940052490 naringin Drugs 0.000 abstract description 23
- 108090000790 Enzymes Proteins 0.000 abstract description 19
- 102000004190 Enzymes Human genes 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 13
- 238000013138 pruning Methods 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 36
- 102220085652 rs864309566 Human genes 0.000 description 18
- 239000007788 liquid Substances 0.000 description 12
- DLIKSSGEMUFQOK-SFTVRKLSSA-N naringenin 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C(C(=O)C[C@H](O2)C=3C=CC(O)=CC=3)C2=C1 DLIKSSGEMUFQOK-SFTVRKLSSA-N 0.000 description 11
- RXVLWCCRHSJBJV-UHFFFAOYSA-N prunin Natural products OCC1OC(O)C(Oc2cc(O)c3C(=O)CC(Oc3c2)c4ccc(O)cc4)C(O)C1O RXVLWCCRHSJBJV-UHFFFAOYSA-N 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- 241000207199 Citrus Species 0.000 description 8
- 235000020971 citrus fruits Nutrition 0.000 description 8
- 239000013612 plasmid Substances 0.000 description 8
- 239000001963 growth medium Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- YAXNATKKPOWVCP-ZLUOBGJFSA-N Ala-Asn-Ala Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O YAXNATKKPOWVCP-ZLUOBGJFSA-N 0.000 description 6
- RAQMSGVCGSJKCL-FOHZUACHSA-N Asn-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC(N)=O RAQMSGVCGSJKCL-FOHZUACHSA-N 0.000 description 6
- XEGZSHSPQNDNRH-JRQIVUDYSA-N Asn-Tyr-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XEGZSHSPQNDNRH-JRQIVUDYSA-N 0.000 description 6
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 6
- SFTZWNJFZYOLBD-ZDLURKLDSA-N Ser-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO SFTZWNJFZYOLBD-ZDLURKLDSA-N 0.000 description 6
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 6
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 6
- 108010087924 alanylproline Proteins 0.000 description 6
- 229930003944 flavone Natural products 0.000 description 6
- 235000011949 flavones Nutrition 0.000 description 6
- 108010089804 glycyl-threonine Proteins 0.000 description 6
- 108010053037 kyotorphin Proteins 0.000 description 6
- 108010051242 phenylalanylserine Proteins 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 5
- 239000000287 crude extract Substances 0.000 description 5
- 150000002212 flavone derivatives Chemical class 0.000 description 5
- 239000007791 liquid phase Substances 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- VWWKKDNCCLAGRM-GVXVVHGQSA-N (2s)-2-[[2-[[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]propanoyl]amino]acetyl]amino]-3-methylbutanoic acid Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O VWWKKDNCCLAGRM-GVXVVHGQSA-N 0.000 description 3
- HXUVTXPOZRFMOY-NSHDSACASA-N 2-[[(2s)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoyl]amino]acetic acid Chemical compound NCC(=O)NCC(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=CC=C1 HXUVTXPOZRFMOY-NSHDSACASA-N 0.000 description 3
- RLMISHABBKUNFO-WHFBIAKZSA-N Ala-Ala-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O RLMISHABBKUNFO-WHFBIAKZSA-N 0.000 description 3
- CXRCVCURMBFFOL-FXQIFTODSA-N Ala-Ala-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O CXRCVCURMBFFOL-FXQIFTODSA-N 0.000 description 3
- GORKKVHIBWAQHM-GCJQMDKQSA-N Ala-Asn-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GORKKVHIBWAQHM-GCJQMDKQSA-N 0.000 description 3
- WDIYWDJLXOCGRW-ACZMJKKPSA-N Ala-Asp-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WDIYWDJLXOCGRW-ACZMJKKPSA-N 0.000 description 3
- BTYTYHBSJKQBQA-GCJQMDKQSA-N Ala-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N)O BTYTYHBSJKQBQA-GCJQMDKQSA-N 0.000 description 3
- ZVFVBBGVOILKPO-WHFBIAKZSA-N Ala-Gly-Ala Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O ZVFVBBGVOILKPO-WHFBIAKZSA-N 0.000 description 3
- BTBUEVAGZCKULD-XPUUQOCRSA-N Ala-Gly-His Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BTBUEVAGZCKULD-XPUUQOCRSA-N 0.000 description 3
- DVJSJDDYCYSMFR-ZKWXMUAHSA-N Ala-Ile-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O DVJSJDDYCYSMFR-ZKWXMUAHSA-N 0.000 description 3
- MNZHHDPWDWQJCQ-YUMQZZPRSA-N Ala-Leu-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O MNZHHDPWDWQJCQ-YUMQZZPRSA-N 0.000 description 3
- OQWQTGBOFPJOIF-DLOVCJGASA-N Ala-Lys-His Chemical compound C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N OQWQTGBOFPJOIF-DLOVCJGASA-N 0.000 description 3
- IHMCQESUJVZTKW-UBHSHLNASA-N Ala-Phe-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 IHMCQESUJVZTKW-UBHSHLNASA-N 0.000 description 3
- XWFWAXPOLRTDFZ-FXQIFTODSA-N Ala-Pro-Ser Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O XWFWAXPOLRTDFZ-FXQIFTODSA-N 0.000 description 3
- AUFACLFHBAGZEN-ZLUOBGJFSA-N Ala-Ser-Cys Chemical compound N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O AUFACLFHBAGZEN-ZLUOBGJFSA-N 0.000 description 3
- MMLHRUJLOUSRJX-CIUDSAMLSA-N Ala-Ser-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN MMLHRUJLOUSRJX-CIUDSAMLSA-N 0.000 description 3
- PEEYDECOOVQKRZ-DLOVCJGASA-N Ala-Ser-Phe Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O PEEYDECOOVQKRZ-DLOVCJGASA-N 0.000 description 3
- YNOCMHZSWJMGBB-GCJQMDKQSA-N Ala-Thr-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O YNOCMHZSWJMGBB-GCJQMDKQSA-N 0.000 description 3
- WNHNMKOFKCHKKD-BFHQHQDPSA-N Ala-Thr-Gly Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O WNHNMKOFKCHKKD-BFHQHQDPSA-N 0.000 description 3
- KTXKIYXZQFWJKB-VZFHVOOUSA-N Ala-Thr-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O KTXKIYXZQFWJKB-VZFHVOOUSA-N 0.000 description 3
- IYKVSFNGSWTTNZ-GUBZILKMSA-N Ala-Val-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IYKVSFNGSWTTNZ-GUBZILKMSA-N 0.000 description 3
- VHAQSYHSDKERBS-XPUUQOCRSA-N Ala-Val-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O VHAQSYHSDKERBS-XPUUQOCRSA-N 0.000 description 3
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 3
- GHNDBBVSWOWYII-LPEHRKFASA-N Arg-Asn-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O GHNDBBVSWOWYII-LPEHRKFASA-N 0.000 description 3
- YWENWUYXQUWRHQ-LPEHRKFASA-N Arg-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O YWENWUYXQUWRHQ-LPEHRKFASA-N 0.000 description 3
- FEZJJKXNPSEYEV-CIUDSAMLSA-N Arg-Gln-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O FEZJJKXNPSEYEV-CIUDSAMLSA-N 0.000 description 3
- HCIUUZGFTDTEGM-NAKRPEOUSA-N Arg-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N HCIUUZGFTDTEGM-NAKRPEOUSA-N 0.000 description 3
- OGSQONVYSTZIJB-WDSOQIARSA-N Arg-Leu-Trp Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCN=C(N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O OGSQONVYSTZIJB-WDSOQIARSA-N 0.000 description 3
- BECXEHHOZNFFFX-IHRRRGAJSA-N Arg-Ser-Tyr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O BECXEHHOZNFFFX-IHRRRGAJSA-N 0.000 description 3
- ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-N 0.000 description 3
- XRNXPIGJPQHCPC-RCWTZXSCSA-N Arg-Thr-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)O)C(O)=O XRNXPIGJPQHCPC-RCWTZXSCSA-N 0.000 description 3
- ZUVMUOOHJYNJPP-XIRDDKMYSA-N Arg-Trp-Gln Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZUVMUOOHJYNJPP-XIRDDKMYSA-N 0.000 description 3
- VLIJAPRTSXSGFY-STQMWFEESA-N Arg-Tyr-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 VLIJAPRTSXSGFY-STQMWFEESA-N 0.000 description 3
- GOVUDFOGXOONFT-VEVYYDQMSA-N Asn-Arg-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GOVUDFOGXOONFT-VEVYYDQMSA-N 0.000 description 3
- OKZOABJQOMAYEC-NUMRIWBASA-N Asn-Gln-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OKZOABJQOMAYEC-NUMRIWBASA-N 0.000 description 3
- GFFRWIJAFFMQGM-NUMRIWBASA-N Asn-Glu-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GFFRWIJAFFMQGM-NUMRIWBASA-N 0.000 description 3
- HYQYLOSCICEYTR-YUMQZZPRSA-N Asn-Gly-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O HYQYLOSCICEYTR-YUMQZZPRSA-N 0.000 description 3
- WQLJRNRLHWJIRW-KKUMJFAQSA-N Asn-His-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC(=O)N)N)O WQLJRNRLHWJIRW-KKUMJFAQSA-N 0.000 description 3
- PNHQRQTVBRDIEF-CIUDSAMLSA-N Asn-Leu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)N)N PNHQRQTVBRDIEF-CIUDSAMLSA-N 0.000 description 3
- YVXRYLVELQYAEQ-SRVKXCTJSA-N Asn-Leu-Lys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N YVXRYLVELQYAEQ-SRVKXCTJSA-N 0.000 description 3
- NCFJQJRLQJEECD-NHCYSSNCSA-N Asn-Leu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O NCFJQJRLQJEECD-NHCYSSNCSA-N 0.000 description 3
- OOXUBGLNDRGOKT-FXQIFTODSA-N Asn-Ser-Arg Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O OOXUBGLNDRGOKT-FXQIFTODSA-N 0.000 description 3
- HPNDKUOLNRVRAY-BIIVOSGPSA-N Asn-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N)C(=O)O HPNDKUOLNRVRAY-BIIVOSGPSA-N 0.000 description 3
- KBQOUDLMWYWXNP-YDHLFZDLSA-N Asn-Val-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CC(=O)N)N KBQOUDLMWYWXNP-YDHLFZDLSA-N 0.000 description 3
- XOQYDFCQPWAMSA-KKHAAJSZSA-N Asn-Val-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOQYDFCQPWAMSA-KKHAAJSZSA-N 0.000 description 3
- SNAWMGHSCHKSDK-GUBZILKMSA-N Asp-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC(=O)O)N SNAWMGHSCHKSDK-GUBZILKMSA-N 0.000 description 3
- DXQOQMCLWWADMU-ACZMJKKPSA-N Asp-Gln-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O DXQOQMCLWWADMU-ACZMJKKPSA-N 0.000 description 3
- POTCZYQVVNXUIG-BQBZGAKWSA-N Asp-Gly-Pro Chemical compound OC(=O)C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O POTCZYQVVNXUIG-BQBZGAKWSA-N 0.000 description 3
- SNDBKTFJWVEVPO-WHFBIAKZSA-N Asp-Gly-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SNDBKTFJWVEVPO-WHFBIAKZSA-N 0.000 description 3
- PCJOFZYFFMBZKC-PCBIJLKTSA-N Asp-Phe-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O PCJOFZYFFMBZKC-PCBIJLKTSA-N 0.000 description 3
- QSFHZPQUAAQHAQ-CIUDSAMLSA-N Asp-Ser-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O QSFHZPQUAAQHAQ-CIUDSAMLSA-N 0.000 description 3
- JDDYEZGPYBBPBN-JRQIVUDYSA-N Asp-Thr-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O JDDYEZGPYBBPBN-JRQIVUDYSA-N 0.000 description 3
- MRYDJCIIVRXVGG-QEJZJMRPSA-N Asp-Trp-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O MRYDJCIIVRXVGG-QEJZJMRPSA-N 0.000 description 3
- OYSYWMMZGJSQRB-AVGNSLFASA-N Asp-Tyr-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O OYSYWMMZGJSQRB-AVGNSLFASA-N 0.000 description 3
- XWKBWZXGNXTDKY-ZKWXMUAHSA-N Asp-Val-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O XWKBWZXGNXTDKY-ZKWXMUAHSA-N 0.000 description 3
- XMKXONRMGJXCJV-LAEOZQHASA-N Asp-Val-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O XMKXONRMGJXCJV-LAEOZQHASA-N 0.000 description 3
- SKSJPIBFNFPTJB-NKWVEPMBSA-N Cys-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CS)N)C(=O)O SKSJPIBFNFPTJB-NKWVEPMBSA-N 0.000 description 3
- LYSHSHHDBVKJRN-JBDRJPRFSA-N Cys-Ile-Ala Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CS)N LYSHSHHDBVKJRN-JBDRJPRFSA-N 0.000 description 3
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 3
- KZEUVLLVULIPNX-GUBZILKMSA-N Gln-Asp-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N KZEUVLLVULIPNX-GUBZILKMSA-N 0.000 description 3
- LPYPANUXJGFMGV-FXQIFTODSA-N Gln-Gln-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N LPYPANUXJGFMGV-FXQIFTODSA-N 0.000 description 3
- IVCOYUURLWQDJQ-LPEHRKFASA-N Gln-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O IVCOYUURLWQDJQ-LPEHRKFASA-N 0.000 description 3
- HSHCEAUPUPJPTE-JYJNAYRXSA-N Gln-Leu-Tyr Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N HSHCEAUPUPJPTE-JYJNAYRXSA-N 0.000 description 3
- SXFPZRRVWSUYII-KBIXCLLPSA-N Gln-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)N)N SXFPZRRVWSUYII-KBIXCLLPSA-N 0.000 description 3
- OTQSTOXRUBVWAP-NRPADANISA-N Gln-Ser-Val Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O OTQSTOXRUBVWAP-NRPADANISA-N 0.000 description 3
- PAOHIZNRJNIXQY-XQXXSGGOSA-N Gln-Thr-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(O)=O PAOHIZNRJNIXQY-XQXXSGGOSA-N 0.000 description 3
- WTJIWXMJESRHMM-XDTLVQLUSA-N Gln-Tyr-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(O)=O WTJIWXMJESRHMM-XDTLVQLUSA-N 0.000 description 3
- UTKUTMJSWKKHEM-WDSKDSINSA-N Glu-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O UTKUTMJSWKKHEM-WDSKDSINSA-N 0.000 description 3
- BUAKRRKDHSSIKK-IHRRRGAJSA-N Glu-Glu-Tyr Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BUAKRRKDHSSIKK-IHRRRGAJSA-N 0.000 description 3
- HILMIYALTUQTRC-XVKPBYJWSA-N Glu-Gly-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O HILMIYALTUQTRC-XVKPBYJWSA-N 0.000 description 3
- ZCFNZTVIDMLUQC-SXNHZJKMSA-N Glu-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCC(=O)O)N ZCFNZTVIDMLUQC-SXNHZJKMSA-N 0.000 description 3
- WIKMTDVSCUJIPJ-CIUDSAMLSA-N Glu-Ser-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N WIKMTDVSCUJIPJ-CIUDSAMLSA-N 0.000 description 3
- VNCNWQPIQYAMAK-ACZMJKKPSA-N Glu-Ser-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O VNCNWQPIQYAMAK-ACZMJKKPSA-N 0.000 description 3
- CQGBSALYGOXQPE-HTUGSXCWSA-N Glu-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N)O CQGBSALYGOXQPE-HTUGSXCWSA-N 0.000 description 3
- DLISPGXMKZTWQG-IFFSRLJSSA-N Glu-Thr-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O DLISPGXMKZTWQG-IFFSRLJSSA-N 0.000 description 3
- UUTGYDAKPISJAO-JYJNAYRXSA-N Glu-Tyr-Leu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 UUTGYDAKPISJAO-JYJNAYRXSA-N 0.000 description 3
- HQTDNEZTGZUWSY-XVKPBYJWSA-N Glu-Val-Gly Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCC(O)=O)C(=O)NCC(O)=O HQTDNEZTGZUWSY-XVKPBYJWSA-N 0.000 description 3
- KKBWDNZXYLGJEY-UHFFFAOYSA-N Gly-Arg-Pro Natural products NCC(=O)NC(CCNC(=N)N)C(=O)N1CCCC1C(=O)O KKBWDNZXYLGJEY-UHFFFAOYSA-N 0.000 description 3
- VXKCPBPQEKKERH-IUCAKERBSA-N Gly-Arg-Pro Chemical compound NC(N)=NCCC[C@H](NC(=O)CN)C(=O)N1CCC[C@H]1C(O)=O VXKCPBPQEKKERH-IUCAKERBSA-N 0.000 description 3
- AIJAPFVDBFYNKN-WHFBIAKZSA-N Gly-Asn-Asp Chemical compound C([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)CN)C(=O)N AIJAPFVDBFYNKN-WHFBIAKZSA-N 0.000 description 3
- GNPVTZJUUBPZKW-WDSKDSINSA-N Gly-Gln-Ser Chemical compound [H]NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GNPVTZJUUBPZKW-WDSKDSINSA-N 0.000 description 3
- XPJBQTCXPJNIFE-ZETCQYMHSA-N Gly-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)CN XPJBQTCXPJNIFE-ZETCQYMHSA-N 0.000 description 3
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 3
- PAWIVEIWWYGBAM-YUMQZZPRSA-N Gly-Leu-Ala Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O PAWIVEIWWYGBAM-YUMQZZPRSA-N 0.000 description 3
- YTSVAIMKVLZUDU-YUMQZZPRSA-N Gly-Leu-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YTSVAIMKVLZUDU-YUMQZZPRSA-N 0.000 description 3
- UHPAZODVFFYEEL-QWRGUYRKSA-N Gly-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)CN UHPAZODVFFYEEL-QWRGUYRKSA-N 0.000 description 3
- FHQRLHFYVZAQHU-IUCAKERBSA-N Gly-Lys-Gln Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(O)=O FHQRLHFYVZAQHU-IUCAKERBSA-N 0.000 description 3
- OQQKUTVULYLCDG-ONGXEEELSA-N Gly-Lys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)CN)C(O)=O OQQKUTVULYLCDG-ONGXEEELSA-N 0.000 description 3
- WMGHDYWNHNLGBV-ONGXEEELSA-N Gly-Phe-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 WMGHDYWNHNLGBV-ONGXEEELSA-N 0.000 description 3
- JPVGHHQGKPQYIL-KBPBESRZSA-N Gly-Phe-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CC=CC=C1 JPVGHHQGKPQYIL-KBPBESRZSA-N 0.000 description 3
- IEGFSKKANYKBDU-QWHCGFSZSA-N Gly-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)CN)C(=O)O IEGFSKKANYKBDU-QWHCGFSZSA-N 0.000 description 3
- GGAPHLIUUTVYMX-QWRGUYRKSA-N Gly-Phe-Ser Chemical compound OC[C@@H](C([O-])=O)NC(=O)[C@@H](NC(=O)C[NH3+])CC1=CC=CC=C1 GGAPHLIUUTVYMX-QWRGUYRKSA-N 0.000 description 3
- OHUKZZYSJBKFRR-WHFBIAKZSA-N Gly-Ser-Asp Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O OHUKZZYSJBKFRR-WHFBIAKZSA-N 0.000 description 3
- JQFILXICXLDTRR-FBCQKBJTSA-N Gly-Thr-Gly Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)NCC(O)=O JQFILXICXLDTRR-FBCQKBJTSA-N 0.000 description 3
- TVTZEOHWHUVYCG-KYNKHSRBSA-N Gly-Thr-Thr Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O TVTZEOHWHUVYCG-KYNKHSRBSA-N 0.000 description 3
- WSWWTQYHFCBKBT-DVJZZOLTSA-N Gly-Thr-Trp Chemical compound C[C@@H](O)[C@H](NC(=O)CN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O WSWWTQYHFCBKBT-DVJZZOLTSA-N 0.000 description 3
- OCRQUYDOYKCOQG-IRXDYDNUSA-N Gly-Tyr-Phe Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=C(O)C=C1 OCRQUYDOYKCOQG-IRXDYDNUSA-N 0.000 description 3
- SYOJVRNQCXYEOV-XVKPBYJWSA-N Gly-Val-Glu Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O SYOJVRNQCXYEOV-XVKPBYJWSA-N 0.000 description 3
- MUGLKCQHTUFLGF-WPRPVWTQSA-N Gly-Val-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)CN MUGLKCQHTUFLGF-WPRPVWTQSA-N 0.000 description 3
- IZVICCORZOSGPT-JSGCOSHPSA-N Gly-Val-Tyr Chemical compound [H]NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O IZVICCORZOSGPT-JSGCOSHPSA-N 0.000 description 3
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 3
- IPIVXQQRZXEUGW-UWJYBYFXSA-N His-Ala-His Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1NC=NC=1)C(O)=O)C1=CN=CN1 IPIVXQQRZXEUGW-UWJYBYFXSA-N 0.000 description 3
- HXKZJLWGSWQKEA-LSJOCFKGSA-N His-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CN=CN1 HXKZJLWGSWQKEA-LSJOCFKGSA-N 0.000 description 3
- YADRBUZBKHHDAO-XPUUQOCRSA-N His-Gly-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](C)C(O)=O YADRBUZBKHHDAO-XPUUQOCRSA-N 0.000 description 3
- VBOFRJNDIOPNDO-YUMQZZPRSA-N His-Gly-Asn Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)N)C(=O)O)N VBOFRJNDIOPNDO-YUMQZZPRSA-N 0.000 description 3
- KHUFDBQXGLEIHC-BZSNNMDCSA-N His-Leu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CN=CN1 KHUFDBQXGLEIHC-BZSNNMDCSA-N 0.000 description 3
- JGFWUKYIQAEYAH-DCAQKATOSA-N His-Ser-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O JGFWUKYIQAEYAH-DCAQKATOSA-N 0.000 description 3
- DEMIXZCKUXVEBO-BWAGICSOSA-N His-Thr-Tyr Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)O DEMIXZCKUXVEBO-BWAGICSOSA-N 0.000 description 3
- YKRYHWJRQUSTKG-KBIXCLLPSA-N Ile-Ala-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YKRYHWJRQUSTKG-KBIXCLLPSA-N 0.000 description 3
- QLRMMMQNCWBNPQ-QXEWZRGKSA-N Ile-Arg-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)O)N QLRMMMQNCWBNPQ-QXEWZRGKSA-N 0.000 description 3
- YOTNPRLPIPHQSB-XUXIUFHCSA-N Ile-Arg-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOTNPRLPIPHQSB-XUXIUFHCSA-N 0.000 description 3
- HDODQNPMSHDXJT-GHCJXIJMSA-N Ile-Asn-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O HDODQNPMSHDXJT-GHCJXIJMSA-N 0.000 description 3
- DCQMJRSOGCYKTR-GHCJXIJMSA-N Ile-Asp-Ser Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O DCQMJRSOGCYKTR-GHCJXIJMSA-N 0.000 description 3
- ZDNORQNHCJUVOV-KBIXCLLPSA-N Ile-Gln-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O ZDNORQNHCJUVOV-KBIXCLLPSA-N 0.000 description 3
- QHGBCRCMBCWMBJ-UHFFFAOYSA-N Ile-Glu-Ala-Lys Natural products CCC(C)C(N)C(=O)NC(CCC(O)=O)C(=O)NC(C)C(=O)NC(C(O)=O)CCCCN QHGBCRCMBCWMBJ-UHFFFAOYSA-N 0.000 description 3
- NZOCIWKZUVUNDW-ZKWXMUAHSA-N Ile-Gly-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@@H](C)C(O)=O NZOCIWKZUVUNDW-ZKWXMUAHSA-N 0.000 description 3
- YGDWPQCLFJNMOL-MNXVOIDGSA-N Ile-Leu-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N YGDWPQCLFJNMOL-MNXVOIDGSA-N 0.000 description 3
- PMMMQRVUMVURGJ-XUXIUFHCSA-N Ile-Leu-Pro Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O PMMMQRVUMVURGJ-XUXIUFHCSA-N 0.000 description 3
- AKOYRLRUFBZOSP-BJDJZHNGSA-N Ile-Lys-Ser Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)O)N AKOYRLRUFBZOSP-BJDJZHNGSA-N 0.000 description 3
- XMYURPUVJSKTMC-KBIXCLLPSA-N Ile-Ser-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N XMYURPUVJSKTMC-KBIXCLLPSA-N 0.000 description 3
- RQJUKVXWAKJDBW-SVSWQMSJSA-N Ile-Ser-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N RQJUKVXWAKJDBW-SVSWQMSJSA-N 0.000 description 3
- RCFDOSNHHZGBOY-UHFFFAOYSA-N L-isoleucyl-L-alanine Natural products CCC(C)C(N)C(=O)NC(C)C(O)=O RCFDOSNHHZGBOY-UHFFFAOYSA-N 0.000 description 3
- 241000880493 Leptailurus serval Species 0.000 description 3
- KSZCCRIGNVSHFH-UWVGGRQHSA-N Leu-Arg-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O KSZCCRIGNVSHFH-UWVGGRQHSA-N 0.000 description 3
- OIARJGNVARWKFP-YUMQZZPRSA-N Leu-Asn-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O OIARJGNVARWKFP-YUMQZZPRSA-N 0.000 description 3
- ILJREDZFPHTUIE-GUBZILKMSA-N Leu-Asp-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O ILJREDZFPHTUIE-GUBZILKMSA-N 0.000 description 3
- WQWSMEOYXJTFRU-GUBZILKMSA-N Leu-Glu-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O WQWSMEOYXJTFRU-GUBZILKMSA-N 0.000 description 3
- LLBQJYDYOLIQAI-JYJNAYRXSA-N Leu-Glu-Tyr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O LLBQJYDYOLIQAI-JYJNAYRXSA-N 0.000 description 3
- HVJVUYQWFYMGJS-GVXVVHGQSA-N Leu-Glu-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O HVJVUYQWFYMGJS-GVXVVHGQSA-N 0.000 description 3
- UCDHVOALNXENLC-KBPBESRZSA-N Leu-Gly-Tyr Chemical compound CC(C)C[C@H]([NH3+])C(=O)NCC(=O)N[C@H](C([O-])=O)CC1=CC=C(O)C=C1 UCDHVOALNXENLC-KBPBESRZSA-N 0.000 description 3
- KOSWSHVQIVTVQF-ZPFDUUQYSA-N Leu-Ile-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O KOSWSHVQIVTVQF-ZPFDUUQYSA-N 0.000 description 3
- IEWBEPKLKUXQBU-VOAKCMCISA-N Leu-Leu-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IEWBEPKLKUXQBU-VOAKCMCISA-N 0.000 description 3
- UCBPDSYUVAAHCD-UWVGGRQHSA-N Leu-Pro-Gly Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O UCBPDSYUVAAHCD-UWVGGRQHSA-N 0.000 description 3
- PWPBLZXWFXJFHE-RHYQMDGZSA-N Leu-Pro-Thr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O PWPBLZXWFXJFHE-RHYQMDGZSA-N 0.000 description 3
- IZPVWNSAVUQBGP-CIUDSAMLSA-N Leu-Ser-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IZPVWNSAVUQBGP-CIUDSAMLSA-N 0.000 description 3
- JIHDFWWRYHSAQB-GUBZILKMSA-N Leu-Ser-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O JIHDFWWRYHSAQB-GUBZILKMSA-N 0.000 description 3
- SVBJIZVVYJYGLA-DCAQKATOSA-N Leu-Ser-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O SVBJIZVVYJYGLA-DCAQKATOSA-N 0.000 description 3
- VDIARPPNADFEAV-WEDXCCLWSA-N Leu-Thr-Gly Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O VDIARPPNADFEAV-WEDXCCLWSA-N 0.000 description 3
- WUHBLPVELFTPQK-KKUMJFAQSA-N Leu-Tyr-Asn Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O WUHBLPVELFTPQK-KKUMJFAQSA-N 0.000 description 3
- BGGTYDNTOYRTTR-MEYUZBJRSA-N Leu-Tyr-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)NC(=O)[C@H](CC(C)C)N)O BGGTYDNTOYRTTR-MEYUZBJRSA-N 0.000 description 3
- YQFZRHYZLARWDY-IHRRRGAJSA-N Leu-Val-Lys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN YQFZRHYZLARWDY-IHRRRGAJSA-N 0.000 description 3
- FZIJIFCXUCZHOL-CIUDSAMLSA-N Lys-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN FZIJIFCXUCZHOL-CIUDSAMLSA-N 0.000 description 3
- RVOMPSJXSRPFJT-DCAQKATOSA-N Lys-Ala-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O RVOMPSJXSRPFJT-DCAQKATOSA-N 0.000 description 3
- AAORVPFVUIHEAB-YUMQZZPRSA-N Lys-Asp-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O AAORVPFVUIHEAB-YUMQZZPRSA-N 0.000 description 3
- ZXEUFAVXODIPHC-GUBZILKMSA-N Lys-Glu-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZXEUFAVXODIPHC-GUBZILKMSA-N 0.000 description 3
- GCMWRRQAKQXDED-IUCAKERBSA-N Lys-Glu-Gly Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)N[C@@H](CCC([O-])=O)C(=O)NCC([O-])=O GCMWRRQAKQXDED-IUCAKERBSA-N 0.000 description 3
- HQXSFFSLXFHWOX-IXOXFDKPSA-N Lys-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCCCN)N)O HQXSFFSLXFHWOX-IXOXFDKPSA-N 0.000 description 3
- JHNOXVASMSXSNB-WEDXCCLWSA-N Lys-Thr-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O JHNOXVASMSXSNB-WEDXCCLWSA-N 0.000 description 3
- VVURYEVJJTXWNE-ULQDDVLXSA-N Lys-Tyr-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O VVURYEVJJTXWNE-ULQDDVLXSA-N 0.000 description 3
- QQPMHUCGDRJFQK-RHYQMDGZSA-N Met-Thr-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QQPMHUCGDRJFQK-RHYQMDGZSA-N 0.000 description 3
- YIGCDRZMZNDENK-UNQGMJICSA-N Met-Thr-Phe Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O YIGCDRZMZNDENK-UNQGMJICSA-N 0.000 description 3
- IIHMNTBFPMRJCN-RCWTZXSCSA-N Met-Val-Thr Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IIHMNTBFPMRJCN-RCWTZXSCSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 3
- XZFYRXDAULDNFX-UHFFFAOYSA-N N-L-cysteinyl-L-phenylalanine Natural products SCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XZFYRXDAULDNFX-UHFFFAOYSA-N 0.000 description 3
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 3
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 3
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 3
- LJUUGSWZPQOJKD-JYJNAYRXSA-N Phe-Arg-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O LJUUGSWZPQOJKD-JYJNAYRXSA-N 0.000 description 3
- KIEPQOIQHFKQLK-PCBIJLKTSA-N Phe-Asn-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KIEPQOIQHFKQLK-PCBIJLKTSA-N 0.000 description 3
- IUVYJBMTHARMIP-PCBIJLKTSA-N Phe-Asp-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O IUVYJBMTHARMIP-PCBIJLKTSA-N 0.000 description 3
- JWQWPTLEOFNCGX-AVGNSLFASA-N Phe-Glu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 JWQWPTLEOFNCGX-AVGNSLFASA-N 0.000 description 3
- NPLGQVKZFGJWAI-QWHCGFSZSA-N Phe-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CC2=CC=CC=C2)N)C(=O)O NPLGQVKZFGJWAI-QWHCGFSZSA-N 0.000 description 3
- YTILBRIUASDGBL-BZSNNMDCSA-N Phe-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 YTILBRIUASDGBL-BZSNNMDCSA-N 0.000 description 3
- TXJJXEXCZBHDNA-ACRUOGEOSA-N Phe-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC3=CN=CN3)C(=O)O)N TXJJXEXCZBHDNA-ACRUOGEOSA-N 0.000 description 3
- FENSZYFJQOFSQR-FIRPJDEBSA-N Phe-Phe-Ile Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FENSZYFJQOFSQR-FIRPJDEBSA-N 0.000 description 3
- GPLWGAYGROGDEN-BZSNNMDCSA-N Phe-Phe-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O GPLWGAYGROGDEN-BZSNNMDCSA-N 0.000 description 3
- KLYYKKGCPOGDPE-OEAJRASXSA-N Phe-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O KLYYKKGCPOGDPE-OEAJRASXSA-N 0.000 description 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 3
- APKRGYLBSCWJJP-FXQIFTODSA-N Pro-Ala-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(O)=O APKRGYLBSCWJJP-FXQIFTODSA-N 0.000 description 3
- DRVIASBABBMZTF-GUBZILKMSA-N Pro-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@@H]1CCCN1 DRVIASBABBMZTF-GUBZILKMSA-N 0.000 description 3
- ZCXQTRXYZOSGJR-FXQIFTODSA-N Pro-Asp-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O ZCXQTRXYZOSGJR-FXQIFTODSA-N 0.000 description 3
- AFXCXDQNRXTSBD-FJXKBIBVSA-N Pro-Gly-Thr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O AFXCXDQNRXTSBD-FJXKBIBVSA-N 0.000 description 3
- AJBQTGZIZQXBLT-STQMWFEESA-N Pro-Phe-Gly Chemical compound C([C@@H](C(=O)NCC(=O)O)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 AJBQTGZIZQXBLT-STQMWFEESA-N 0.000 description 3
- WHNJMTHJGCEKGA-ULQDDVLXSA-N Pro-Phe-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O WHNJMTHJGCEKGA-ULQDDVLXSA-N 0.000 description 3
- BGWKULMLUIUPKY-BQBZGAKWSA-N Pro-Ser-Gly Chemical compound OC(=O)CNC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 BGWKULMLUIUPKY-BQBZGAKWSA-N 0.000 description 3
- IURWWZYKYPEANQ-HJGDQZAQSA-N Pro-Thr-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O IURWWZYKYPEANQ-HJGDQZAQSA-N 0.000 description 3
- AIOWVDNPESPXRB-YTWAJWBKSA-N Pro-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2)O AIOWVDNPESPXRB-YTWAJWBKSA-N 0.000 description 3
- NBDHWLZEMKSVHH-UVBJJODRSA-N Pro-Trp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@@H]3CCCN3 NBDHWLZEMKSVHH-UVBJJODRSA-N 0.000 description 3
- DYJTXTCEXMCPBF-UFYCRDLUSA-N Pro-Tyr-Phe Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)O DYJTXTCEXMCPBF-UFYCRDLUSA-N 0.000 description 3
- XVAUJOAYHWWNQF-ZLUOBGJFSA-N Ser-Asn-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O XVAUJOAYHWWNQF-ZLUOBGJFSA-N 0.000 description 3
- VGNYHOBZJKWRGI-CIUDSAMLSA-N Ser-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CO VGNYHOBZJKWRGI-CIUDSAMLSA-N 0.000 description 3
- UGJRQLURDVGULT-LKXGYXEUSA-N Ser-Asn-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UGJRQLURDVGULT-LKXGYXEUSA-N 0.000 description 3
- WBINSDOPZHQPPM-AVGNSLFASA-N Ser-Glu-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N)O WBINSDOPZHQPPM-AVGNSLFASA-N 0.000 description 3
- MUARUIBTKQJKFY-WHFBIAKZSA-N Ser-Gly-Asp Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MUARUIBTKQJKFY-WHFBIAKZSA-N 0.000 description 3
- UIGMAMGZOJVTDN-WHFBIAKZSA-N Ser-Gly-Ser Chemical compound OC[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O UIGMAMGZOJVTDN-WHFBIAKZSA-N 0.000 description 3
- LQESNKGTTNHZPZ-GHCJXIJMSA-N Ser-Ile-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O LQESNKGTTNHZPZ-GHCJXIJMSA-N 0.000 description 3
- KCGIREHVWRXNDH-GARJFASQSA-N Ser-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N KCGIREHVWRXNDH-GARJFASQSA-N 0.000 description 3
- MUJQWSAWLLRJCE-KATARQTJSA-N Ser-Leu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MUJQWSAWLLRJCE-KATARQTJSA-N 0.000 description 3
- VIIJCAQMJBHSJH-FXQIFTODSA-N Ser-Met-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(O)=O VIIJCAQMJBHSJH-FXQIFTODSA-N 0.000 description 3
- UGTZYIPOBYXWRW-SRVKXCTJSA-N Ser-Phe-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O UGTZYIPOBYXWRW-SRVKXCTJSA-N 0.000 description 3
- BMKNXTJLHFIAAH-CIUDSAMLSA-N Ser-Ser-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O BMKNXTJLHFIAAH-CIUDSAMLSA-N 0.000 description 3
- PYTKULIABVRXSC-BWBBJGPYSA-N Ser-Ser-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PYTKULIABVRXSC-BWBBJGPYSA-N 0.000 description 3
- VGQVAVQWKJLIRM-FXQIFTODSA-N Ser-Ser-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O VGQVAVQWKJLIRM-FXQIFTODSA-N 0.000 description 3
- DYEGLQRVMBWQLD-IXOXFDKPSA-N Ser-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CO)N)O DYEGLQRVMBWQLD-IXOXFDKPSA-N 0.000 description 3
- VLMIUSLQONKLDV-HEIBUPTGSA-N Ser-Thr-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VLMIUSLQONKLDV-HEIBUPTGSA-N 0.000 description 3
- WMZVVNLPHFSUPA-BPUTZDHNSA-N Ser-Trp-Arg Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)=CNC2=C1 WMZVVNLPHFSUPA-BPUTZDHNSA-N 0.000 description 3
- PCMZJFMUYWIERL-ZKWXMUAHSA-N Ser-Val-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O PCMZJFMUYWIERL-ZKWXMUAHSA-N 0.000 description 3
- LLSLRQOEAFCZLW-NRPADANISA-N Ser-Val-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LLSLRQOEAFCZLW-NRPADANISA-N 0.000 description 3
- MFQMZDPAZRZAPV-NAKRPEOUSA-N Ser-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)N MFQMZDPAZRZAPV-NAKRPEOUSA-N 0.000 description 3
- YEDSOSIKVUMIJE-DCAQKATOSA-N Ser-Val-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O YEDSOSIKVUMIJE-DCAQKATOSA-N 0.000 description 3
- ANOQEBQWIAYIMV-AEJSXWLSSA-N Ser-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N ANOQEBQWIAYIMV-AEJSXWLSSA-N 0.000 description 3
- CEXFELBFVHLYDZ-XGEHTFHBSA-N Thr-Arg-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CEXFELBFVHLYDZ-XGEHTFHBSA-N 0.000 description 3
- YBXMGKCLOPDEKA-NUMRIWBASA-N Thr-Asp-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YBXMGKCLOPDEKA-NUMRIWBASA-N 0.000 description 3
- OYTNZCBFDXGQGE-XQXXSGGOSA-N Thr-Gln-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C)C(=O)O)N)O OYTNZCBFDXGQGE-XQXXSGGOSA-N 0.000 description 3
- JMGJDTNUMAZNLX-RWRJDSDZSA-N Thr-Glu-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JMGJDTNUMAZNLX-RWRJDSDZSA-N 0.000 description 3
- KBBRNEDOYWMIJP-KYNKHSRBSA-N Thr-Gly-Thr Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KBBRNEDOYWMIJP-KYNKHSRBSA-N 0.000 description 3
- RRRRCRYTLZVCEN-HJGDQZAQSA-N Thr-Leu-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O RRRRCRYTLZVCEN-HJGDQZAQSA-N 0.000 description 3
- UUSQVWOVUYMLJA-PPCPHDFISA-N Thr-Lys-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O UUSQVWOVUYMLJA-PPCPHDFISA-N 0.000 description 3
- GIBPOCDKBPNRJB-HSHDSVGOSA-N Thr-Met-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O GIBPOCDKBPNRJB-HSHDSVGOSA-N 0.000 description 3
- FWTFAZKJORVTIR-VZFHVOOUSA-N Thr-Ser-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O FWTFAZKJORVTIR-VZFHVOOUSA-N 0.000 description 3
- AHERARIZBPOMNU-KATARQTJSA-N Thr-Ser-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O AHERARIZBPOMNU-KATARQTJSA-N 0.000 description 3
- KVEWWQRTAVMOFT-KJEVXHAQSA-N Thr-Tyr-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O KVEWWQRTAVMOFT-KJEVXHAQSA-N 0.000 description 3
- QNXZCKMXHPULME-ZNSHCXBVSA-N Thr-Val-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N)O QNXZCKMXHPULME-ZNSHCXBVSA-N 0.000 description 3
- BRBCKMMXKONBAA-KWBADKCTSA-N Trp-Ala-Ala Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(O)=O)=CNC2=C1 BRBCKMMXKONBAA-KWBADKCTSA-N 0.000 description 3
- MJBBMTOGSOSAKJ-HJXMPXNTSA-N Trp-Ala-Ile Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MJBBMTOGSOSAKJ-HJXMPXNTSA-N 0.000 description 3
- DVWAIHZOPSYMSJ-ZVZYQTTQSA-N Trp-Glu-Val Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O)=CNC2=C1 DVWAIHZOPSYMSJ-ZVZYQTTQSA-N 0.000 description 3
- HLDFBNPSURDYEN-VHWLVUOQSA-N Trp-Ile-Asp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N HLDFBNPSURDYEN-VHWLVUOQSA-N 0.000 description 3
- NLWCSMOXNKBRLC-WDSOQIARSA-N Trp-Lys-Val Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O NLWCSMOXNKBRLC-WDSOQIARSA-N 0.000 description 3
- DYIXEGROAOVQPK-VFAJRCTISA-N Trp-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O DYIXEGROAOVQPK-VFAJRCTISA-N 0.000 description 3
- YXSSXUIBUJGHJY-SFJXLCSZSA-N Trp-Thr-Phe Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)[C@H](O)C)C(O)=O)C1=CC=CC=C1 YXSSXUIBUJGHJY-SFJXLCSZSA-N 0.000 description 3
- CRCHQCUINSOGFD-JBACZVJFSA-N Trp-Tyr-Glu Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC3=CC=C(C=C3)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N CRCHQCUINSOGFD-JBACZVJFSA-N 0.000 description 3
- DXYWRYQRKPIGGU-BPNCWPANSA-N Tyr-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DXYWRYQRKPIGGU-BPNCWPANSA-N 0.000 description 3
- AKFLVKKWVZMFOT-IHRRRGAJSA-N Tyr-Arg-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O AKFLVKKWVZMFOT-IHRRRGAJSA-N 0.000 description 3
- IIJWXEUNETVJPV-IHRRRGAJSA-N Tyr-Arg-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N)O IIJWXEUNETVJPV-IHRRRGAJSA-N 0.000 description 3
- NGALWFGCOMHUSN-AVGNSLFASA-N Tyr-Gln-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NGALWFGCOMHUSN-AVGNSLFASA-N 0.000 description 3
- QAYSODICXVZUIA-WLTAIBSBSA-N Tyr-Gly-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O QAYSODICXVZUIA-WLTAIBSBSA-N 0.000 description 3
- ULHJJQYGMWONTD-HKUYNNGSSA-N Tyr-Gly-Trp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O ULHJJQYGMWONTD-HKUYNNGSSA-N 0.000 description 3
- XJPXTYLVMUZGNW-IHRRRGAJSA-N Tyr-Pro-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O XJPXTYLVMUZGNW-IHRRRGAJSA-N 0.000 description 3
- LVFZXRQQQDTBQH-IRIUXVKKSA-N Tyr-Thr-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(O)=O LVFZXRQQQDTBQH-IRIUXVKKSA-N 0.000 description 3
- KSGKJSFPWSMJHK-JNPHEJMOSA-N Tyr-Tyr-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KSGKJSFPWSMJHK-JNPHEJMOSA-N 0.000 description 3
- RVGVIWNHABGIFH-IHRRRGAJSA-N Tyr-Val-Ser Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O RVGVIWNHABGIFH-IHRRRGAJSA-N 0.000 description 3
- SLLKXDSRVAOREO-KZVJFYERSA-N Val-Ala-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)N)O SLLKXDSRVAOREO-KZVJFYERSA-N 0.000 description 3
- KKHRWGYHBZORMQ-NHCYSSNCSA-N Val-Arg-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KKHRWGYHBZORMQ-NHCYSSNCSA-N 0.000 description 3
- COYSIHFOCOMGCF-UHFFFAOYSA-N Val-Arg-Gly Natural products CC(C)C(N)C(=O)NC(C(=O)NCC(O)=O)CCCN=C(N)N COYSIHFOCOMGCF-UHFFFAOYSA-N 0.000 description 3
- OGNMURQZFMHFFD-NHCYSSNCSA-N Val-Asn-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N OGNMURQZFMHFFD-NHCYSSNCSA-N 0.000 description 3
- PVPAOIGJYHVWBT-KKHAAJSZSA-N Val-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)N)O PVPAOIGJYHVWBT-KKHAAJSZSA-N 0.000 description 3
- CFSSLXZJEMERJY-NRPADANISA-N Val-Gln-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O CFSSLXZJEMERJY-NRPADANISA-N 0.000 description 3
- HURRXSNHCCSJHA-AUTRQRHGSA-N Val-Gln-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N HURRXSNHCCSJHA-AUTRQRHGSA-N 0.000 description 3
- CPTQYHDSVGVGDZ-UKJIMTQDSA-N Val-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C(C)C)N CPTQYHDSVGVGDZ-UKJIMTQDSA-N 0.000 description 3
- WNZSAUMKZQXHNC-UKJIMTQDSA-N Val-Ile-Gln Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N WNZSAUMKZQXHNC-UKJIMTQDSA-N 0.000 description 3
- UMPVMAYCLYMYGA-ONGXEEELSA-N Val-Leu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O UMPVMAYCLYMYGA-ONGXEEELSA-N 0.000 description 3
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-N 0.000 description 3
- 108010005233 alanylglutamic acid Proteins 0.000 description 3
- 108010047495 alanylglycine Proteins 0.000 description 3
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 description 3
- 108010062796 arginyllysine Proteins 0.000 description 3
- 108010036533 arginylvaline Proteins 0.000 description 3
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 3
- 108010093581 aspartyl-proline Proteins 0.000 description 3
- 108010047857 aspartylglycine Proteins 0.000 description 3
- 108010092854 aspartyllysine Proteins 0.000 description 3
- 108010068265 aspartyltyrosine Proteins 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 229930003935 flavonoid Natural products 0.000 description 3
- 150000002215 flavonoids Chemical class 0.000 description 3
- 235000017173 flavonoids Nutrition 0.000 description 3
- 108010078144 glutaminyl-glycine Proteins 0.000 description 3
- 108010008237 glutamyl-valyl-glycine Proteins 0.000 description 3
- 108010049041 glutamylalanine Proteins 0.000 description 3
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 3
- 108010075431 glycyl-alanyl-phenylalanine Proteins 0.000 description 3
- 108010072405 glycyl-aspartyl-glycine Proteins 0.000 description 3
- 108010045126 glycyl-tyrosyl-glycine Proteins 0.000 description 3
- 108010010147 glycylglutamine Proteins 0.000 description 3
- 108010020688 glycylhistidine Proteins 0.000 description 3
- 108010050848 glycylleucine Proteins 0.000 description 3
- 108010081551 glycylphenylalanine Proteins 0.000 description 3
- 108010084389 glycyltryptophan Proteins 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 108010085325 histidylproline Proteins 0.000 description 3
- 108010009932 leucyl-alanyl-glycyl-valine Proteins 0.000 description 3
- 108010051673 leucyl-glycyl-phenylalanine Proteins 0.000 description 3
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 108010016686 methionyl-alanyl-serine Proteins 0.000 description 3
- 108010005942 methionylglycine Proteins 0.000 description 3
- 108010084572 phenylalanyl-valine Proteins 0.000 description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 3
- 229960002965 pravastatin Drugs 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 108010031719 prolyl-serine Proteins 0.000 description 3
- 108010053725 prolylvaline Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 3
- 108010026333 seryl-proline Proteins 0.000 description 3
- 108010061238 threonyl-glycine Proteins 0.000 description 3
- 108010038745 tryptophylglycine Proteins 0.000 description 3
- 108010005834 tyrosyl-alanyl-glycine Proteins 0.000 description 3
- 108010020532 tyrosyl-proline Proteins 0.000 description 3
- 108010003137 tyrosyltyrosine Proteins 0.000 description 3
- 108010009962 valyltyrosine Proteins 0.000 description 3
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 241001506991 Komagataella phaffii GS115 Species 0.000 description 2
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 2
- REJBPZVUHYNMEN-LSJOCFKGSA-N Val-Ala-His Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](C(C)C)N REJBPZVUHYNMEN-LSJOCFKGSA-N 0.000 description 2
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 238000010170 biological method Methods 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- -1 flavone glycosides Chemical class 0.000 description 2
- 229930182486 flavonoid glycoside Natural products 0.000 description 2
- 108010074027 glycyl-seryl-phenylalanine Proteins 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 1
- 241000228232 Aspergillus tubingensis Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 description 1
- 241000235058 Komagataella pastoris Species 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- OQWNEUXPKHIEJO-NRPADANISA-N Val-Glu-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)O)N OQWNEUXPKHIEJO-NRPADANISA-N 0.000 description 1
- VSCIANXXVZOYOC-AVGNSLFASA-N Val-Pro-His Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N VSCIANXXVZOYOC-AVGNSLFASA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- PNNNRSAQSRJVSB-BXKVDMCESA-N aldehydo-L-rhamnose Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O PNNNRSAQSRJVSB-BXKVDMCESA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 description 1
- 230000003570 biosynthesizing effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 description 1
- 239000013599 cloning vector Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 150000007955 flavonoid glycosides Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 description 1
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 description 1
- 229940025878 hesperidin Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000007852 inverse PCR Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 238000012257 pre-denaturation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/44—Preparation of O-glycosides, e.g. glucosides
- C12P19/60—Preparation of O-glycosides, e.g. glucosides having an oxygen of the saccharide radical directly bound to a non-saccharide heterocyclic ring or a condensed ring system containing a non-saccharide heterocyclic ring, e.g. coumermycin, novobiocin
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/0104—Alpha-L-rhamnosidase (3.2.1.40)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明提供了一种α‑L‑鼠李糖苷酶突变体及其应用，该突变体是由如SEQ ID NO.1所示序列的野生型α‑L‑鼠李糖苷酶经过其第37或165位氨基酸突变而产生的突变体。与野生型α‑L‑鼠李糖苷酶相比，该突变体的酶活性得到了一定的提高，并且可高效专一的转化柚皮苷制备普鲁宁。
Description
技术领域
本发明属于生物工程技术领域，具体涉及一种α-L-鼠李糖苷酶突变体及其在制备普鲁宁中的应用。
背景技术
普鲁宁是一种具有降低胆固醇、抗氧化及抗病毒等功效的黄酮苷类物质，在食品和药物方面有很好的应用前景。普鲁宁在自然界中的丰度较低，难以从生物组织中提取制备。目前制备普鲁宁主要有化学法和生物法，化学法在高温高压条件，使柚皮苷去掉糖基，该方法需要大量的化学催化剂而且反应条件一般比较激烈，得到的产品副产物多，分离纯化困难。生物法是利用α-L-鼠李糖苷酶水解柚皮苷转化为普鲁宁，该方法反应条件温和，对品质影响小，且纯度高、转化率快。
α-L-鼠李糖苷酶能特异性水解许多天然产物的末端α-L-鼠李糖基，可作用于黄酮糖苷类物质中α-1、α-1,2、α-1,3、α-1,4、α-1,6糖苷键连接的L-鼠李糖。该酶广泛存在于植物、动物和微生物中，可用于柑橘类果汁的脱苦、生物合成普鲁宁和鼠李糖、增加酒的香味、去除橙子果汁中的橙皮苷晶体及提高黄酮的生物活性等。在利用α-L-鼠李糖苷酶水解柑橘黄酮粗提物中的柚皮苷制备普鲁宁中，因为柑橘黄酮粗提物中含有多种黄酮糖苷类化合物，使得产物中不仅产生普鲁宁，还会有其它副产物生成。以柑橘黄酮粗提物为原料制备普鲁宁，需先纯化成柚皮苷，再经过α-L-鼠李糖苷酶水解，进一步纯化为普鲁宁，需要经过2次纯化及2次浓缩结晶才能制备得到普鲁宁，该工艺复杂，得率低。
发明内容
本发明旨在至少在一定程度上解决上述技术中的技术问题之一。为此，本发明提出了一种α-L-鼠李糖苷酶突变体，其可高效专一的转化柚皮苷制备普鲁宁。
为此，在本发明的第一个方面中，提供了α-L-鼠李糖苷酶突变体，由如SEQ IDNO.1所示序列的野生型α-L-鼠李糖苷酶经过其第37或165位氨基酸突变而产生的突变体。
根据本发明的实施例，所述突变体是将野生型卡拉胶酶的第37或第165位氨基酸进行突变。与野生型α-L-鼠李糖苷酶相比，突变体A37P的酶活是WT的245％，突变体G165E的酶活是WT的176％。二者均可特异性转化柚皮苷生成普鲁宁，没有其它副产物生成，转化率大幅度提高，其中A37P酶活高达8.5IU/ml，在80℃、pH7.0、底物浓度75g/L的反应条件下，转化率达73.51％。G165E酶活高达6IU/ml，在80℃、pH7.0、底物浓度75g/L的反应条件下，转化率达69.45％。该方法具有操作简单、成本低廉等优点，大大降低了生产成本，具有广阔的应用前景。
可选地，第37位氨基酸突变对应的突变体的氨基酸序列如SEQ ID NO:2所示；第165位氨基酸突变对应的突变体的氨基酸序列如SEQ ID NO:3所示。
在本发明的第二方面中，提供了一种编码上述α-L-鼠李糖苷酶突变体的基因，第37位氨基酸突变对应的突变体的核苷酸序列如SEQ ID NO:4所示；第165位氨基酸突变对应的突变体的核苷酸序列如SEQ ID NO:5所示。
在本发明的第三个方面中，提供了一种构建体，其包含编码上述α-L-鼠李糖苷酶突变体的基因。
在本发明的第四个方面中，提供了上述α-L-鼠李糖苷酶突变体在制备普鲁宁中的应用。
本发明的附加方面和优点将在下面的描述中部分给出，部分将从下面的描述中变得明显，或通过本发明的实践了解到。
附图说明
图1为SDS-PAGE分析结果，其中，M：分子量标准蛋白；1：纯化后的AT-Rha；2：纯化后的突变体A37P；3：纯化后的突变体G165E；
图2为高效液相色谱测得不同柚皮苷浓度下的峰面积绘制的标准曲线；
图3为AT-Rha、A37P、G165E的酶活；
图4为实施例3中柚皮苷标品的液相色谱图；
图5为实施例3中普鲁宁标品的液相色谱图；
图6为实施例3中柑橘黄酮粗提物样品的液相色谱图；
图7为实施例3中WT反应结束后体系中柚皮苷和普鲁宁的液相色谱图；
图8为实施例3中A37P反应结束后体系中柚皮苷和普鲁宁的液相色谱图；
图9为实施例3中G165E反应结束后体系中柚皮苷和普鲁宁的液相色谱图。
具体实施方式
下面详细描述本发明的实施例，所述实施例的示例在附图中示出，其中自始至终相同或类似的标号表示相同或类似的元件或具有相同或类似功能的元件。下面通过参考附图描述的实施例是示例性的，旨在用于解释本发明，而不能理解为对本发明的限制。
下文的公开提供了许多不同的实施例或例子用来实现本发明的不同实施方式。为了简化本发明的公开，下文中对特定实施例或示例进行描述。当然，他们仅仅为示例，并且目的不在于限制本发明。此外，本发明提供的各种特定工艺和材料的例子，本领域普通技术人员可以意识到其他工艺的可应用性和/或其他材料的使用。除非另有说明，本发明的实施将采用本领域技术人员的能力范围之内的化学、分子生物学等领域的传统技术。另外，除非另有说明，在本文中，核酸以5’至3’的方向从左向右书写，氨基酸序列则以氨基端到羧基端的方向从左向右书写。
下面通过说明性的具体实施例对本发明进行描述，这些实施例并不以任何方式限制本发明的范围。特别说明的是：本发明所用到的试剂除特别说明外均有市售。
实施例1构建α-L-鼠李糖苷酶突变体A37P、G165E
重组克隆载体的构建：
以塔宾曲霉TS529来源的α-L-鼠李糖苷酶AT-Rha为模板制备突变体。α-L-鼠李糖苷酶AT-Rha的基因核酸序列如SEQ ID NO:1所示，该基因编码的蛋白氨基酸序列如SEQ IDNO:2所示。将含有编码α-L鼠李糖苷酶AT-Rha的基因的菌株pPIC9K-AT-Rha在含1‰Amp抗性的LB平板上活化，37℃培养18h，挑取单菌落于同样含1‰Amp抗性的50mL LB锥形瓶中，37℃180rpm培养至OD600为1.0，按照天根生化科技有限公司的质粒小提试剂盒说明书提取质粒。
提取的质粒作为模板，使用TOYOBO公司的KOD-Plus-Mutagenesis Kit点突变试剂盒完成突变质粒的构建。突变质粒的构建参照KOD-Plus-Mutagenesis Kit说明书共有三个步骤，包括反向PCR、Dpn Ⅰ消化模板以及PCR产物的自身环化。
表1突变引物表
反向PCR反应体系及反应过程如下：
表1反向PCR体系
PCR条件为：94℃预变性2min，98℃变性10s，68℃延伸11min，11个循环，4℃保存。
Dpn I消化模板反应体系及反应过程如下：PCR反应液中加入1μL Dpn I，在37℃下反应1h。
PCR产物的自身环化反应体系及反应过程如下：
表3 PCR产物自身环化体系
反应条件：16℃下反应1h。
将上述构建好的突变质粒全部转入大肠杆菌DH5α感受态，混匀后置于冰上30min，结束后将大肠杆菌DH5α感受态放入温度42℃下热激90s后置于冰上缓和2min，再加入1mL未添加Amp的LB培养基，结束后将大肠杆菌DH5α感受态放于37℃下2h，结束后取菌体200μL涂布于含1‰Amp的LB培养基上，于37℃恒温培养箱培养直至长出单菌落。
待长出单菌落后挑取单菌落于含同样抗性的LB试管中37℃180rpm培养过夜。通过菌液PCR进行阳性验证，以菌液为模板，分别用通用引物(5’AOX和3’AOX)和特异性引物(AT-F和AT-R)进行PCR反应。
表4菌液PCR反应体系
表5 PCR验证引物表
PCR反应结束后进行琼脂糖凝胶电泳，通用引物和特异引物均扩增出条带的菌送至厦门铂瑞生物科技有限公司测序。
α-L-鼠李糖苷酶突变体A37P、G165E的电转化：
将验证正确的pPIC9K-A37P和pPIC9K-G165E的阳性克隆子提取质粒并使用Pme I将所提质粒线性化。
表6线性化体系
取80μL毕赤酵母感受态与已回收的线性化质粒混匀，采用电击转化法转化至毕赤酵母GS115中，吸取200μL菌体涂于MD培养基上，30℃倒置培养2-3天，直至长出单菌落。随机挑取MD平板的单菌落转接至含G418(终浓度为2.5mg/mL)抗性的YPD平板上，将筛选得到的单菌落活化培养进行鉴定阳性并保种。选择阳性鉴定的毕赤酵母GS115菌株接种到YPD培养基进行培养，培养条件为30℃、转速220rpm，培养时16h。
α-L-鼠李糖苷酶突变体A37P、G165E的表达及纯化：
含有突变型或野生型α-L-鼠李糖苷酶基因的基因工程菌菌液以1％的接种量将活化后的菌株接种到BMGY培养基中，培养至OD600值达到3.0，室温下沉降菌体，倒掉培养基将菌体全部转接到BMMY培养基中，每间隔24h添加500μL甲醇溶液对蛋白进行诱导表达。培养7天后通过冷冻离心机在4℃温度下以5867×g离心15min，保留上清酶液，4℃储存。
收集α-L-鼠李糖苷酶WT及A37P、G165E粗酶液，经50kDa的膜进行超滤浓缩，再经Sephacry S-200HR凝胶柱进行纯化后，通过SDS-PAGE检验，结果如图1所示，WT及突变体酶A37P、G165E均为单一条带，大小为130kDa。
实施例2α-L-鼠李糖苷酶突变体A37P、G165E的酶活测定
使用酶反应缓冲液pH 4.0配制0～250μg/mL的柚皮苷，过0.22μm水系滤膜，进液相瓶，使用岛津液相SPD-20L测定。
表7液相洗脱条件
测定结果如图2所示，以底物浓度为X值，峰面积为Y值绘制标准曲线为Y＝80474X+30101(R2＝0.9999)。
以pH 4.0的300μg/mL柚皮苷为底物，在60℃下孵育10min，加入2μg/mL的酶液(实施例1纯化得的WT、A37P或G165E)在60℃反应30min后沸水浴灭活10min。将反应液过滤进液相瓶，使用岛津液相SPD-20L测定底物柚皮苷的变化从而计算出酶活。测定结果如图3所示，突变体A37P的酶活是WT的245％，突变体G165E的酶活是WT的176％。
实施例3α-L-鼠李糖苷酶突变体A37P、G165E专一性转化柚皮苷生产普鲁宁
以柑橘黄酮粗提物为底物，以WT、A37P、G165E为催化剂，反应条件：柚皮苷浓度75g/L，加酶量3.5～8.5IU/mL，反应温度60℃，pH为4.0下孵育15min。然后，反应液在30000g下离心10min，通过0.22μm膜过滤，在280nm处HPLC分析柑橘黄酮粗提物组成成分及其水解产物普鲁宁的浓度。测定HPLC结果如图4～图9所示，柚皮苷的出峰时间在9.5min左右(图4)，普鲁宁的出峰时间在10.5min左右(图5)。图6显示了柑橘黄酮粗提物样品的组成成分，图7～图9分别为WT、A37P和G165E反应结束后体系中柚皮苷和普鲁宁的液相色谱图。与WT相比，突变体A37P、G165E均可特异性转化柚皮苷，没有其它副产物生成，转化率大幅度提高，WT转化率38.35％，突变体A37P转化率73.51％，突变体G165E转化率69.45％。
综上，根据本发明的实施例，采用定点突变技术将野生酶进行定点突变，得到α-L-鼠李糖苷酶突变体A37P、G165E，发现了突变体具有优良的酶学特性。与WT相比，突变体A37P的酶活是WT的245％，突变体G165E的酶活是WT的176％。且均可特异性转化柚皮苷，没有其它副产物生成，转化率大幅度提高，WT转化率38.35％，突变体A37P转化率73.51％，突变体G165E转化率69.45％。该方法具有操作简单、成本低廉等优点，具有广阔的应用前景。
在本说明书的描述中，参考术语“一个实施例”、“一些实施例”、“示例”、“具体示例”、或“一些示例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本发明的至少一个实施例或示例中。在本说明书中，对上述术语的示意性表述不应理解为必须针对的是相同的实施例或示例。而且，描述的具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。此外，本领域的技术人员可以将本说明书中描述的不同实施例或示例进行接合和组合。
尽管上面已经示出和描述了本发明的实施例，可以理解的是，上述实施例是示例性的，不能理解为对本发明的限制，本领域的普通技术人员在本发明的范围内可以对上述实施例进行变化、修改、替换和变型。
SEQUENCE LISTING
<110> 集美大学
<120> 一种α-L-鼠李糖苷酶突变体及其在制备普鲁宁中的应用
<130> 无
<160> 5
<170> PatentIn version 3.5
<210> 1
<211> 888
<212> PRT
<213> 人工序列（Artificial sequence）
<400> 1
Met Ala Ala Leu Glu Glu Ala Arg Arg Asn Asp Thr Leu Thr Ala Ile
1 5 10 15
Lys Glu Asn Val Arg Glu Ala Ile Gly His Leu Tyr Val Gln Gln Leu
20 25 30
Ala Val Arg Val Ala His Arg Cys Pro Lys Ala Arg Lys His Thr Asp
35 40 45
Pro Ser Gly Ser Val Ile Ala Asp Glu Ile Asn Ser Glu Thr Val Val
50 55 60
Leu Pro Thr Arg Tyr Gly Thr Ser Leu Gly Phe Ala Asn Tyr Thr Gln
65 70 75 80
His Gly Asn Ala Ser Cys Phe Thr Leu Asp Gln Lys Ser Ser Leu Ile
85 90 95
Thr Leu Asp Tyr Gly Thr Glu Val Gly Gly Phe Pro Phe Phe His Val
100 105 110
Asp Ser Leu Ser Asn Ala Val Gln Ile Glu Ala Lys Tyr Thr Glu Ser
115 120 125
Lys Thr Gly Leu Asp Glu Pro Phe Gly Asp Gly Pro Trp Thr Phe Ser
130 135 140
Asn Gly Leu Ser Asn Thr Phe Arg Val Glu Thr Phe Asn Val Thr Ser
145 150 155 160
Pro Gly Thr Val Gly Ser Phe Phe Ile Gln Gly Gly Leu Arg Trp Gln
165 170 175
Asn Leu Lys Leu Leu Thr Asp Gly Ser Val Arg Ile Cys Glu Ala Gly
180 185 190
Ile Lys Ser Gly Asn Asp Arg Thr Pro Val Asn Lys Leu Pro Gly Phe
195 200 205
Phe Glu Ser Ser Asn Lys Leu Tyr Asn Glu Ile Trp Ala Leu Gly Pro
210 215 220
Arg Thr Val Gln Gln Ala Cys Ile Ala Ala Asp Thr Ala Pro Ser Thr
225 230 235 240
Trp Glu Val Thr Asp Glu Gly Val Tyr Leu Arg Gly Gln Gln Pro Ala
245 250 255
Gln Ser Val Ala Gly Ala Ser Phe Asp Asn Tyr Thr Met Thr Phe Gln
260 265 270
Thr Lys Ile Ile Arg Gly Gly Thr Gly Trp Lys Val Ala Ala Gly Val
275 280 285
Gly Gly Phe Gly Pro Tyr Phe Val Leu Thr Ser Glu Tyr Pro Ala Asp
290 295 300
Ser Thr Phe Val Asn Thr Asn Arg Thr Thr Val Pro Ala Asn Thr Leu
305 310 315 320
Ala Val Gly Tyr Gly Trp Asn Leu Val Asn Gln Thr Ser Leu Thr Thr
325 330 335
Gly Lys Val Asn His Tyr Ser Leu Pro Phe Asn Ile Lys Glu Gly Glu
340 345 350
Trp Tyr Glu Ile Ser Thr Ser Ile Asn Ala Thr Gly Tyr Ala Val Thr
355 360 365
Ile Asn Gly Thr Glu Thr Phe Val Ala Leu Asp Asp Leu Gln Ile Val
370 375 380
Ser Gly Thr Thr Gly Ser Ser Gly Ser Leu Thr Gly Gly Thr Trp Gly
385 390 395 400
Phe Gly Pro Tyr Gln Asp Gln Thr Ala Leu Val Lys Asp Val Glu Val
405 410 415
Ile Ala Gln Asn Gly Thr Gln Leu Tyr Arg Asn Pro Met Thr Leu Ser
420 425 430
Ser Val Leu Glu Glu Tyr Gly Val Met Ala Ser Lys His Ser Val Cys
435 440 445
Leu Asp Gly Ala Lys Arg Asp Arg Leu Val Trp Asn Gly Asp Phe Val
450 455 460
His Thr Tyr Arg Val Ile Gln Ser Ser Thr Tyr Arg Ser Asp Phe Ile
465 470 475 480
Thr Gly Ser Leu Glu Tyr Trp Ile Asp Arg Gln Ala Pro Asp Ser Ser
485 490 495
Gln Tyr Ala Gly Tyr Phe Ser Met Ser Pro Ala Met Gly Gln Ser Ala
500 505 510
Lys Tyr Val Asp Thr Tyr Ala Ser Phe Gly Leu Leu Asp Tyr Gln Leu
515 520 525
Phe Leu Leu Asn Val Phe Ala Gly His Tyr Arg Asn Ser Gly Asp Lys
530 535 540
Ala Phe Val Ala Lys His Trp Thr Lys Ile Arg Lys Gly Val Glu Ala
545 550 555 560
Ile Leu Pro Leu Ile Asp Asp Gln Ser Gly Leu Ala Val Ala Thr Asn
565 570 575
Ile Gly Ala Phe Phe Ser Gly Ser Asp Asn Gly Thr Ala Val Ser Gly
580 585 590
Leu Leu Ala His Thr Leu Asp Gln Met Ala Asp Val Ala Ser Ala Met
595 600 605
Asn Glu Thr Asp Val Ala Thr Met Trp Thr Arg Ser Ala Thr Ser Ile
610 615 620
Lys Ala Ala Ile Ser Gln Arg Leu Trp Asn Ser Arg Leu Gly Tyr Tyr
625 630 635 640
Ala Thr Asp Leu Ser Asp Pro Thr Glu Gln Ser Ile Thr Gly Thr Ala
645 650 655
Trp Ala Ile Leu Ala Gly Val Ala Asn Ala Thr Gln Ala Glu Ser Ser
660 665 670
Leu Ala Ala Leu Ser Ser Leu Arg Leu Gly Ile Gly Tyr Lys Thr Ser
675 680 685
Ser Ser Val Ala Asn Ala Ser Thr Thr Asn Leu Ala Pro Phe Leu Thr
690 695 700
Gly Phe Leu Leu Glu Ser Ile Leu Gln Glu Ser Arg Asn Ser Pro Asn
705 710 715 720
Ser Ser Gln Ala Arg Ser Thr Ala Ile Ser Val Leu Leu Asp Gln Leu
725 730 735
Trp Ala Ala Met Val Thr Gln Asp Lys Tyr Tyr Thr Gly Thr Thr Trp
740 745 750
Glu Tyr Leu Tyr Pro Asp Gly Arg Pro Gly Leu Asp Leu Tyr Thr Ser
755 760 765
His Ala His Pro Trp Ala Ala Ala Pro Thr Tyr Val Leu Ser Glu Tyr
770 775 780
Val Leu Gly Val Gln Ala Thr Ser Ala Gly Phe Ser Asp Trp Glu Phe
785 790 795 800
Arg Pro Ala Met Leu Asp Val Asn Val Ser Trp Ala Arg Gly Arg Val
805 810 815
Pro Thr Pro His Gly Ala Ile Gln Ala Ser Trp Arg Leu Asn Gly Thr
820 825 830
Ser Val Gln Leu Ser Val Cys Gly Pro Ser Gly Thr Glu Gly Val Val
835 840 845
Ser Val Pro Phe Asp Ile Arg Ser Tyr Ser Val Asn Gly Lys Gln Gln
850 855 860
Ile Asp Ser Lys Asp Gly Leu Glu Val Tyr Val Ser Gly Gly Ser Cys
865 870 875 880
Thr Glu Ile His Ala Val Arg Gly
885
<210> 2
<211> 888
<212> PRT
<213> 人工序列（Artificial sequence）
<400> 2
Met Ala Ala Leu Glu Glu Ala Arg Arg Asn Asp Thr Leu Thr Ala Ile
1 5 10 15
Lys Glu Asn Val Arg Glu Ala Ile Gly His Leu Tyr Val Gln Gln Leu
20 25 30
Ala Val Arg Val Pro His Arg Cys Pro Lys Ala Arg Lys His Thr Asp
35 40 45
Pro Ser Gly Ser Val Ile Ala Asp Glu Ile Asn Ser Glu Thr Val Val
50 55 60
Leu Pro Thr Arg Tyr Gly Thr Ser Leu Gly Phe Ala Asn Tyr Thr Gln
65 70 75 80
His Gly Asn Ala Ser Cys Phe Thr Leu Asp Gln Lys Ser Ser Leu Ile
85 90 95
Thr Leu Asp Tyr Gly Thr Glu Val Gly Gly Phe Pro Phe Phe His Val
100 105 110
Asp Ser Leu Ser Asn Ala Val Gln Ile Glu Ala Lys Tyr Thr Glu Ser
115 120 125
Lys Thr Gly Leu Asp Glu Pro Phe Gly Asp Gly Pro Trp Thr Phe Ser
130 135 140
Asn Gly Leu Ser Asn Thr Phe Arg Val Glu Thr Phe Asn Val Thr Ser
145 150 155 160
Pro Gly Thr Val Gly Ser Phe Phe Ile Gln Gly Gly Leu Arg Trp Gln
165 170 175
Asn Leu Lys Leu Leu Thr Asp Gly Ser Val Arg Ile Cys Glu Ala Gly
180 185 190
Ile Lys Ser Gly Asn Asp Arg Thr Pro Val Asn Lys Leu Pro Gly Phe
195 200 205
Phe Glu Ser Ser Asn Lys Leu Tyr Asn Glu Ile Trp Ala Leu Gly Pro
210 215 220
Arg Thr Val Gln Gln Ala Cys Ile Ala Ala Asp Thr Ala Pro Ser Thr
225 230 235 240
Trp Glu Val Thr Asp Glu Gly Val Tyr Leu Arg Gly Gln Gln Pro Ala
245 250 255
Gln Ser Val Ala Gly Ala Ser Phe Asp Asn Tyr Thr Met Thr Phe Gln
260 265 270
Thr Lys Ile Ile Arg Gly Gly Thr Gly Trp Lys Val Ala Ala Gly Val
275 280 285
Gly Gly Phe Gly Pro Tyr Phe Val Leu Thr Ser Glu Tyr Pro Ala Asp
290 295 300
Ser Thr Phe Val Asn Thr Asn Arg Thr Thr Val Pro Ala Asn Thr Leu
305 310 315 320
Ala Val Gly Tyr Gly Trp Asn Leu Val Asn Gln Thr Ser Leu Thr Thr
325 330 335
Gly Lys Val Asn His Tyr Ser Leu Pro Phe Asn Ile Lys Glu Gly Glu
340 345 350
Trp Tyr Glu Ile Ser Thr Ser Ile Asn Ala Thr Gly Tyr Ala Val Thr
355 360 365
Ile Asn Gly Thr Glu Thr Phe Val Ala Leu Asp Asp Leu Gln Ile Val
370 375 380
Ser Gly Thr Thr Gly Ser Ser Gly Ser Leu Thr Gly Gly Thr Trp Gly
385 390 395 400
Phe Gly Pro Tyr Gln Asp Gln Thr Ala Leu Val Lys Asp Val Glu Val
405 410 415
Ile Ala Gln Asn Gly Thr Gln Leu Tyr Arg Asn Pro Met Thr Leu Ser
420 425 430
Ser Val Leu Glu Glu Tyr Gly Val Met Ala Ser Lys His Ser Val Cys
435 440 445
Leu Asp Gly Ala Lys Arg Asp Arg Leu Val Trp Asn Gly Asp Phe Val
450 455 460
His Thr Tyr Arg Val Ile Gln Ser Ser Thr Tyr Arg Ser Asp Phe Ile
465 470 475 480
Thr Gly Ser Leu Glu Tyr Trp Ile Asp Arg Gln Ala Pro Asp Ser Ser
485 490 495
Gln Tyr Ala Gly Tyr Phe Ser Met Ser Pro Ala Met Gly Gln Ser Ala
500 505 510
Lys Tyr Val Asp Thr Tyr Ala Ser Phe Gly Leu Leu Asp Tyr Gln Leu
515 520 525
Phe Leu Leu Asn Val Phe Ala Gly His Tyr Arg Asn Ser Gly Asp Lys
530 535 540
Ala Phe Val Ala Lys His Trp Thr Lys Ile Arg Lys Gly Val Glu Ala
545 550 555 560
Ile Leu Pro Leu Ile Asp Asp Gln Ser Gly Leu Ala Val Ala Thr Asn
565 570 575
Ile Gly Ala Phe Phe Ser Gly Ser Asp Asn Gly Thr Ala Val Ser Gly
580 585 590
Leu Leu Ala His Thr Leu Asp Gln Met Ala Asp Val Ala Ser Ala Met
595 600 605
Asn Glu Thr Asp Val Ala Thr Met Trp Thr Arg Ser Ala Thr Ser Ile
610 615 620
Lys Ala Ala Ile Ser Gln Arg Leu Trp Asn Ser Arg Leu Gly Tyr Tyr
625 630 635 640
Ala Thr Asp Leu Ser Asp Pro Thr Glu Gln Ser Ile Thr Gly Thr Ala
645 650 655
Trp Ala Ile Leu Ala Gly Val Ala Asn Ala Thr Gln Ala Glu Ser Ser
660 665 670
Leu Ala Ala Leu Ser Ser Leu Arg Leu Gly Ile Gly Tyr Lys Thr Ser
675 680 685
Ser Ser Val Ala Asn Ala Ser Thr Thr Asn Leu Ala Pro Phe Leu Thr
690 695 700
Gly Phe Leu Leu Glu Ser Ile Leu Gln Glu Ser Arg Asn Ser Pro Asn
705 710 715 720
Ser Ser Gln Ala Arg Ser Thr Ala Ile Ser Val Leu Leu Asp Gln Leu
725 730 735
Trp Ala Ala Met Val Thr Gln Asp Lys Tyr Tyr Thr Gly Thr Thr Trp
740 745 750
Glu Tyr Leu Tyr Pro Asp Gly Arg Pro Gly Leu Asp Leu Tyr Thr Ser
755 760 765
His Ala His Pro Trp Ala Ala Ala Pro Thr Tyr Val Leu Ser Glu Tyr
770 775 780
Val Leu Gly Val Gln Ala Thr Ser Ala Gly Phe Ser Asp Trp Glu Phe
785 790 795 800
Arg Pro Ala Met Leu Asp Val Asn Val Ser Trp Ala Arg Gly Arg Val
805 810 815
Pro Thr Pro His Gly Ala Ile Gln Ala Ser Trp Arg Leu Asn Gly Thr
820 825 830
Ser Val Gln Leu Ser Val Cys Gly Pro Ser Gly Thr Glu Gly Val Val
835 840 845
Ser Val Pro Phe Asp Ile Arg Ser Tyr Ser Val Asn Gly Lys Gln Gln
850 855 860
Ile Asp Ser Lys Asp Gly Leu Glu Val Tyr Val Ser Gly Gly Ser Cys
865 870 875 880
Thr Glu Ile His Ala Val Arg Gly
885
<210> 3
<211> 888
<212> PRT
<213> 人工序列（Artificial sequence）
<400> 3
Met Ala Ala Leu Glu Glu Ala Arg Arg Asn Asp Thr Leu Thr Ala Ile
1 5 10 15
Lys Glu Asn Val Arg Glu Ala Ile Gly His Leu Tyr Val Gln Gln Leu
20 25 30
Ala Val Arg Val Ala His Arg Cys Pro Lys Ala Arg Lys His Thr Asp
35 40 45
Pro Ser Gly Ser Val Ile Ala Asp Glu Ile Asn Ser Glu Thr Val Val
50 55 60
Leu Pro Thr Arg Tyr Gly Thr Ser Leu Gly Phe Ala Asn Tyr Thr Gln
65 70 75 80
His Gly Asn Ala Ser Cys Phe Thr Leu Asp Gln Lys Ser Ser Leu Ile
85 90 95
Thr Leu Asp Tyr Gly Thr Glu Val Gly Gly Phe Pro Phe Phe His Val
100 105 110
Asp Ser Leu Ser Asn Ala Val Gln Ile Glu Ala Lys Tyr Thr Glu Ser
115 120 125
Lys Thr Gly Leu Asp Glu Pro Phe Gly Asp Gly Pro Trp Thr Phe Ser
130 135 140
Asn Gly Leu Ser Asn Thr Phe Arg Val Glu Thr Phe Asn Val Thr Ser
145 150 155 160
Pro Gly Thr Val Glu Ser Phe Phe Ile Gln Gly Gly Leu Arg Trp Gln
165 170 175
Asn Leu Lys Leu Leu Thr Asp Gly Ser Val Arg Ile Cys Glu Ala Gly
180 185 190
Ile Lys Ser Gly Asn Asp Arg Thr Pro Val Asn Lys Leu Pro Gly Phe
195 200 205
Phe Glu Ser Ser Asn Lys Leu Tyr Asn Glu Ile Trp Ala Leu Gly Pro
210 215 220
Arg Thr Val Gln Gln Ala Cys Ile Ala Ala Asp Thr Ala Pro Ser Thr
225 230 235 240
Trp Glu Val Thr Asp Glu Gly Val Tyr Leu Arg Gly Gln Gln Pro Ala
245 250 255
Gln Ser Val Ala Gly Ala Ser Phe Asp Asn Tyr Thr Met Thr Phe Gln
260 265 270
Thr Lys Ile Ile Arg Gly Gly Thr Gly Trp Lys Val Ala Ala Gly Val
275 280 285
Gly Gly Phe Gly Pro Tyr Phe Val Leu Thr Ser Glu Tyr Pro Ala Asp
290 295 300
Ser Thr Phe Val Asn Thr Asn Arg Thr Thr Val Pro Ala Asn Thr Leu
305 310 315 320
Ala Val Gly Tyr Gly Trp Asn Leu Val Asn Gln Thr Ser Leu Thr Thr
325 330 335
Gly Lys Val Asn His Tyr Ser Leu Pro Phe Asn Ile Lys Glu Gly Glu
340 345 350
Trp Tyr Glu Ile Ser Thr Ser Ile Asn Ala Thr Gly Tyr Ala Val Thr
355 360 365
Ile Asn Gly Thr Glu Thr Phe Val Ala Leu Asp Asp Leu Gln Ile Val
370 375 380
Ser Gly Thr Thr Gly Ser Ser Gly Ser Leu Thr Gly Gly Thr Trp Gly
385 390 395 400
Phe Gly Pro Tyr Gln Asp Gln Thr Ala Leu Val Lys Asp Val Glu Val
405 410 415
Ile Ala Gln Asn Gly Thr Gln Leu Tyr Arg Asn Pro Met Thr Leu Ser
420 425 430
Ser Val Leu Glu Glu Tyr Gly Val Met Ala Ser Lys His Ser Val Cys
435 440 445
Leu Asp Gly Ala Lys Arg Asp Arg Leu Val Trp Asn Gly Asp Phe Val
450 455 460
His Thr Tyr Arg Val Ile Gln Ser Ser Thr Tyr Arg Ser Asp Phe Ile
465 470 475 480
Thr Gly Ser Leu Glu Tyr Trp Ile Asp Arg Gln Ala Pro Asp Ser Ser
485 490 495
Gln Tyr Ala Gly Tyr Phe Ser Met Ser Pro Ala Met Gly Gln Ser Ala
500 505 510
Lys Tyr Val Asp Thr Tyr Ala Ser Phe Gly Leu Leu Asp Tyr Gln Leu
515 520 525
Phe Leu Leu Asn Val Phe Ala Gly His Tyr Arg Asn Ser Gly Asp Lys
530 535 540
Ala Phe Val Ala Lys His Trp Thr Lys Ile Arg Lys Gly Val Glu Ala
545 550 555 560
Ile Leu Pro Leu Ile Asp Asp Gln Ser Gly Leu Ala Val Ala Thr Asn
565 570 575
Ile Gly Ala Phe Phe Ser Gly Ser Asp Asn Gly Thr Ala Val Ser Gly
580 585 590
Leu Leu Ala His Thr Leu Asp Gln Met Ala Asp Val Ala Ser Ala Met
595 600 605
Asn Glu Thr Asp Val Ala Thr Met Trp Thr Arg Ser Ala Thr Ser Ile
610 615 620
Lys Ala Ala Ile Ser Gln Arg Leu Trp Asn Ser Arg Leu Gly Tyr Tyr
625 630 635 640
Ala Thr Asp Leu Ser Asp Pro Thr Glu Gln Ser Ile Thr Gly Thr Ala
645 650 655
Trp Ala Ile Leu Ala Gly Val Ala Asn Ala Thr Gln Ala Glu Ser Ser
660 665 670
Leu Ala Ala Leu Ser Ser Leu Arg Leu Gly Ile Gly Tyr Lys Thr Ser
675 680 685
Ser Ser Val Ala Asn Ala Ser Thr Thr Asn Leu Ala Pro Phe Leu Thr
690 695 700
Gly Phe Leu Leu Glu Ser Ile Leu Gln Glu Ser Arg Asn Ser Pro Asn
705 710 715 720
Ser Ser Gln Ala Arg Ser Thr Ala Ile Ser Val Leu Leu Asp Gln Leu
725 730 735
Trp Ala Ala Met Val Thr Gln Asp Lys Tyr Tyr Thr Gly Thr Thr Trp
740 745 750
Glu Tyr Leu Tyr Pro Asp Gly Arg Pro Gly Leu Asp Leu Tyr Thr Ser
755 760 765
His Ala His Pro Trp Ala Ala Ala Pro Thr Tyr Val Leu Ser Glu Tyr
770 775 780
Val Leu Gly Val Gln Ala Thr Ser Ala Gly Phe Ser Asp Trp Glu Phe
785 790 795 800
Arg Pro Ala Met Leu Asp Val Asn Val Ser Trp Ala Arg Gly Arg Val
805 810 815
Pro Thr Pro His Gly Ala Ile Gln Ala Ser Trp Arg Leu Asn Gly Thr
820 825 830
Ser Val Gln Leu Ser Val Cys Gly Pro Ser Gly Thr Glu Gly Val Val
835 840 845
Ser Val Pro Phe Asp Ile Arg Ser Tyr Ser Val Asn Gly Lys Gln Gln
850 855 860
Ile Asp Ser Lys Asp Gly Leu Glu Val Tyr Val Ser Gly Gly Ser Cys
865 870 875 880
Thr Glu Ile His Ala Val Arg Gly
885
<210> 4
<211> 2667
<212> DNA
<213> 人工序列（Artificial sequence）
<400> 4
atggcagcgt tggaggaagc tcgtaggaat gacaccttga cagccataaa ggaaaatgtc 60
cgggaagcga ttggccatct ttacgtgcag cagcttgctg ttcgcgtccc acataggtgc 120
ccaaaggcgc gtaaacatac tgaccctagt ggctcggtta ttgctgacga aattaacagt 180
gagactgtcg tgcttcctac ccgatacgga actagcttgg gatttgcgaa ttatacgcag 240
catggaaacg catcctgctt cacgcttgac cagaaaagct cattgattac cctagactac 300
ggtaccgaag ttgggggatt ccccttcttc catgtggact ctctatccaa tgcagtccag 360
atcgaggcca agtacaccga atccaagacc ggtcttgacg agccgtttgg tgatggccca 420
tggaccttct ccaacggcct ctctaatacc ttccgcgtcg aaacgttcaa tgtcacctca 480
cccgggacag tgggatcctt cttcattcaa gggggccttc gctggcagaa cctcaagctc 540
ctcacagatg gcagtgttcg catatgcgaa gctggtatca aatctggaaa tgaccgcact 600
ccggtaaaca aactgccagg gttcttcgag agctcgaaca agctgtataa tgaaatatgg 660
gccttagggc cacgcacagt ccagcaagca tgcatcgcgg cagataccgc accatcaaca 720
tgggaagtca ctgacgaagg tgtgtatctt cgtggacagc aacctgctca atcagtggca 780
ggagcgtcct ttgacaacta caccatgacc ttccagacca agattatccg tggaggaaca 840
ggttggaagg ttgccgctgg tgtgggcgga tttggtcctt attttgttct taccagcgaa 900
taccctgctg actccacatt tgtcaatacc aaccgaacga ccgtccctgc aaacacacta 960
gctgtgggtt acgggtggaa ccttgtgaat cagacatctc tcaccaccgg aaaagtgaac 1020
cattattcct tacctttcaa cattaaggag ggagaatggt atgagatctc gacttccatc 1080
aatgcgaccg gatatgctgt taccatcaat ggaaccgaga cattcgtggc actggatgac 1140
ctgcaaattg tatctggtac tactggctcc tctggcagtc tgacaggcgg tacctggggg 1200
tttgggccat atcaggatca aaccgctctt gtcaaggacg tggaggtcat cgcacaaaat 1260
ggtacccagt tgtaccggaa tccgatgacg ctcagctccg tcctcgagga atacggagtg 1320
atggccagta agcactccgt ctgtctggac ggtgcgaaaa gggaccgtct tgtctggaat 1380
ggtgattttg tacacactta tcgcgtcatc cagtccagca cctatcgctc cgattttata 1440
accggttccc tagagtactg gatcgaccgt caggcaccag actcgtcgca gtacgctggc 1500
tacttcagca tgtcacctgc tatgggccaa tcggcgaaat atgttgacac gtatgcttct 1560
ttcggacttc ttgattacca gctttttctt ctcaacgtat ttgctggtca ctacagaaac 1620
tctggcgaca aagcgtttgt ggccaagcat tggacaaaga tcaggaaagg cgtggaagcc 1680
atcctgcctt tgatcgatga ccaatctgga ctggccgtcg ccaccaatat cggggcattc 1740
ttctcgggat ccgacaatgg cactgcagta tcggggctcc ttgcccacac actcgaccag 1800
atggctgatg tggcgtccgc gatgaatgag acagatgtcg cgacaatgtg gactcgttcg 1860
gcgacttcaa tcaaagctgc gatcagccag cggctctgga attcccgctt ggggtactat 1920
gcgaccgacc tgagcgaccc gaccgagcag tctatcaccg gcactgcctg ggctattctt 1980
gcgggagtcg ccaatgccac gcaagcagaa tcctccctcg cagcattatc ctctcttcgg 2040
cttggaatag gctacaaaac gtcgagctcc gttgccaacg catcaacgac taatcttgcg 2100
ccttttctca ccggtttcct cttagaatcg attttgcagg agagtcgcaa cagtcccaac 2160
tcaagtcaag ccagatctac cgcaattagc gtgctccttg accaactttg ggctgcgatg 2220
gtgacccagg ataaatacta tactggtaca acttgggaat acctttaccc tgatggccga 2280
cccgggcttg acctctacac gtcgcatgca cacccttggg cagctgcgcc aacgtacgtt 2340
ctgtcggaat atgtcctcgg tgttcaagcg acttcggctg gattttctga ctgggagttt 2400
cgtcccgcga tgttggatgt gaatgtttca tgggcacggg gaagagtgcc cactcctcat 2460
ggggcgatcc aggctagctg gcggttgaat ggcacgagcg tgcagttgag cgtgtgtggc 2520
cctagtggta cagagggagt cgtcagcgtg ccatttgata tcaggtcgta ttcagttaac 2580
ggaaagcaac agatagacag caaggacggc ttggaagtct atgtgtctgg aggatcatgt 2640
actgaaatcc atgccgtcag aggttga 2667
<210> 5
<211> 2667
<212> DNA
<213> 人工序列（Artificial sequence）
<400> 5
atggcagcgt tggaggaagc tcgtaggaat gacaccttga cagccataaa ggaaaatgtc 60
cgggaagcga ttggccatct ttacgtgcag cagcttgctg ttcgcgtcgc tcataggtgc 120
ccaaaggcgc gtaaacatac tgaccctagt ggctcggtta ttgctgacga aattaacagt 180
gagactgtcg tgcttcctac ccgatacgga actagcttgg gatttgcgaa ttatacgcag 240
catggaaacg catcctgctt cacgcttgac cagaaaagct cattgattac cctagactac 300
ggtaccgaag ttgggggatt ccccttcttc catgtggact ctctatccaa tgcagtccag 360
atcgaggcca agtacaccga atccaagacc ggtcttgacg agccgtttgg tgatggccca 420
tggaccttct ccaacggcct ctctaatacc ttccgcgtcg aaacgttcaa tgtcacctca 480
cccgggacag tggagtcctt cttcattcaa gggggccttc gctggcagaa cctcaagctc 540
ctcacagatg gcagtgttcg catatgcgaa gctggtatca aatctggaaa tgaccgcact 600
ccggtaaaca aactgccagg gttcttcgag agctcgaaca agctgtataa tgaaatatgg 660
gccttagggc cacgcacagt ccagcaagca tgcatcgcgg cagataccgc accatcaaca 720
tgggaagtca ctgacgaagg tgtgtatctt cgtggacagc aacctgctca atcagtggca 780
ggagcgtcct ttgacaacta caccatgacc ttccagacca agattatccg tggaggaaca 840
ggttggaagg ttgccgctgg tgtgggcgga tttggtcctt attttgttct taccagcgaa 900
taccctgctg actccacatt tgtcaatacc aaccgaacga ccgtccctgc aaacacacta 960
gctgtgggtt acgggtggaa ccttgtgaat cagacatctc tcaccaccgg aaaagtgaac 1020
cattattcct tacctttcaa cattaaggag ggagaatggt atgagatctc gacttccatc 1080
aatgcgaccg gatatgctgt taccatcaat ggaaccgaga cattcgtggc actggatgac 1140
ctgcaaattg tatctggtac tactggctcc tctggcagtc tgacaggcgg tacctggggg 1200
tttgggccat atcaggatca aaccgctctt gtcaaggacg tggaggtcat cgcacaaaat 1260
ggtacccagt tgtaccggaa tccgatgacg ctcagctccg tcctcgagga atacggagtg 1320
atggccagta agcactccgt ctgtctggac ggtgcgaaaa gggaccgtct tgtctggaat 1380
ggtgattttg tacacactta tcgcgtcatc cagtccagca cctatcgctc cgattttata 1440
accggttccc tagagtactg gatcgaccgt caggcaccag actcgtcgca gtacgctggc 1500
tacttcagca tgtcacctgc tatgggccaa tcggcgaaat atgttgacac gtatgcttct 1560
ttcggacttc ttgattacca gctttttctt ctcaacgtat ttgctggtca ctacagaaac 1620
tctggcgaca aagcgtttgt ggccaagcat tggacaaaga tcaggaaagg cgtggaagcc 1680
atcctgcctt tgatcgatga ccaatctgga ctggccgtcg ccaccaatat cggggcattc 1740
ttctcgggat ccgacaatgg cactgcagta tcggggctcc ttgcccacac actcgaccag 1800
atggctgatg tggcgtccgc gatgaatgag acagatgtcg cgacaatgtg gactcgttcg 1860
gcgacttcaa tcaaagctgc gatcagccag cggctctgga attcccgctt ggggtactat 1920
gcgaccgacc tgagcgaccc gaccgagcag tctatcaccg gcactgcctg ggctattctt 1980
gcgggagtcg ccaatgccac gcaagcagaa tcctccctcg cagcattatc ctctcttcgg 2040
cttggaatag gctacaaaac gtcgagctcc gttgccaacg catcaacgac taatcttgcg 2100
ccttttctca ccggtttcct cttagaatcg attttgcagg agagtcgcaa cagtcccaac 2160
tcaagtcaag ccagatctac cgcaattagc gtgctccttg accaactttg ggctgcgatg 2220
gtgacccagg ataaatacta tactggtaca acttgggaat acctttaccc tgatggccga 2280
cccgggcttg acctctacac gtcgcatgca cacccttggg cagctgcgcc aacgtacgtt 2340
ctgtcggaat atgtcctcgg tgttcaagcg acttcggctg gattttctga ctgggagttt 2400
cgtcccgcga tgttggatgt gaatgtttca tgggcacggg gaagagtgcc cactcctcat 2460
ggggcgatcc aggctagctg gcggttgaat ggcacgagcg tgcagttgag cgtgtgtggc 2520
cctagtggta cagagggagt cgtcagcgtg ccatttgata tcaggtcgta ttcagttaac 2580
ggaaagcaac agatagacag caaggacggc ttggaagtct atgtgtctgg aggatcatgt 2640
actgaaatcc atgccgtcag aggttga 2667
Claims (5)
1.一种α-L-鼠李糖苷酶突变体，其特征在于，由如SEQ ID NO.1所示序列的野生型α-L-鼠李糖苷酶经过其第37或165位氨基酸突变而产生的突变体。
2.如权利要求1所述的α-L-鼠李糖苷酶突变体，其特征在于，第37位氨基酸突变对应的突变体的氨基酸序列如SEQ ID NO:2所示；第165位氨基酸突变对应的突变体的氨基酸序列如SEQ ID NO:3所示。
3.一种编码权利要求1或2所述的α-L-鼠李糖苷酶突变体的基因，其特征在于，第37位氨基酸突变对应的突变体的核苷酸序列如SEQ ID NO:4所示；第165位氨基酸突变对应的突变体的核苷酸序列如SEQ ID NO:5所示。
4.一种构建体，其特征在于，包含如权利要求3所述的基因。
5.如权利要求1或2所述的α-L-鼠李糖苷酶突变体在制备普鲁宁中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111144381.7A CN113736762B (zh) | 2021-09-28 | 2021-09-28 | 一种α-L-鼠李糖苷酶突变体及其在制备普鲁宁中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111144381.7A CN113736762B (zh) | 2021-09-28 | 2021-09-28 | 一种α-L-鼠李糖苷酶突变体及其在制备普鲁宁中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113736762A true CN113736762A (zh) | 2021-12-03 |
| CN113736762B CN113736762B (zh) | 2023-09-12 |
Family
ID=78741617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111144381.7A Active CN113736762B (zh) | 2021-09-28 | 2021-09-28 | 一种α-L-鼠李糖苷酶突变体及其在制备普鲁宁中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113736762B (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115094106A (zh) * | 2022-06-29 | 2022-09-23 | 四川大学 | 一种普鲁宁的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111676207A (zh) * | 2019-07-09 | 2020-09-18 | 中国林业科学研究院林产化学工业研究所 | 一种α-鼠李糖苷酶、其编码基因及其表达和应用 |
| CN112592912A (zh) * | 2021-01-07 | 2021-04-02 | 云南与诺生物工程有限责任公司 | 糖苷酶及其编码基因和它们的应用 |
-
2021
- 2021-09-28 CN CN202111144381.7A patent/CN113736762B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111676207A (zh) * | 2019-07-09 | 2020-09-18 | 中国林业科学研究院林产化学工业研究所 | 一种α-鼠李糖苷酶、其编码基因及其表达和应用 |
| CN112592912A (zh) * | 2021-01-07 | 2021-04-02 | 云南与诺生物工程有限责任公司 | 糖苷酶及其编码基因和它们的应用 |
Non-Patent Citations (4)
| Title |
|---|
| LIJUN LI等: "An effective computational-screening strategy for simultaneously improving both catalytic activity and thermostability of α-l-rhamnosidase", BIOTECHNOL BIOENG, vol. 118, no. 9, pages 3409 - 3419 * |
| LIJUN LI等: "Enhancement in affinity of Aspergillus niger JMU-TS528 α-L-rhamnosidase (r-Rha1) by semiconservative site-directed mutagenesis of (α/α) catalytic domain", INT J BIOL MACROMOL, vol. 151, pages 845 - 854, XP086143038, DOI: 10.1016/j.ijbiomac.2020.02.157 * |
| LIJUN LI等: "Heterologous Expression and Characterization of a New Clade of Aspergillus α‑L-Rhamnosidase Suitable for Citrus Juice Processing", J. AGRIC. FOOD CHEM, vol. 67, pages 2926 - 2935 * |
| 刘嘉男: "计算机辅助模拟、设计和分析α-L-鼠李糖苷酶结构域的功能", 中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑, no. 01, pages 024 - 517 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115094106A (zh) * | 2022-06-29 | 2022-09-23 | 四川大学 | 一种普鲁宁的制备方法 |
| CN115094106B (zh) * | 2022-06-29 | 2023-07-04 | 四川大学 | 一种普鲁宁的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113736762B (zh) | 2023-09-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112063666B (zh) | 一种重组蔗糖异构酶在转化蔗糖制备异麦芽酮糖中的应用 | |
| CN113151203B (zh) | 一种生物催化合成香兰素的单加氧酶的突变体及应用 | |
| CN109988799A (zh) | 一种甘油-2-α-葡萄糖基化酶在制备2-α-甘油葡萄糖苷中的应用 | |
| CN113862290B (zh) | 一种来源于甘草的异黄酮4′-o-甲基转移酶及其应用 | |
| CN113088528A (zh) | 一种α-L-鼠李糖苷酶突变酶、基因及表达制备方法 | |
| CN104388411A (zh) | 一种琼胶酶及其基因和应用 | |
| CN108884120A (zh) | 用于通过使用微生物纯化3，6-脱水-l-半乳糖的新颖方法 | |
| CN104789539A (zh) | 一种海藻糖合酶的突变体及其制备方法和应用 | |
| CN111454918B (zh) | 一种烯醇还原酶突变体及其在制备(r)-香茅醛中的应用 | |
| CN110423787B (zh) | 一种均一性褐藻三糖的制备方法 | |
| CN113801240B (zh) | 一种d-阿洛酮糖-3-差向异构酶活性聚集体及其制备方法与应用 | |
| CN113736762A (zh) | 一种α-L-鼠李糖苷酶突变体及其在制备普鲁宁中的应用 | |
| CN110592045B (zh) | 一种重组酯酶、基因、工程菌及拆分(r,s)-吲哚啉-2-甲酸乙酯的应用 | |
| CN104877983A (zh) | 一种海藻糖合酶突变体及其制备与应用 | |
| CN112980815A (zh) | α-L-岩藻糖苷酶OUCJdch-16及其应用 | |
| CN109402080B (zh) | 蛋白质ugt142及其编码基因与应用 | |
| CN113736766B (zh) | 胶原蛋白水解酶及其编码基因、制备方法和用途 | |
| CN108251406B (zh) | L-鼠李树胶糖-1-磷酸醛缩酶及其在催化合成稀有糖d-阿洛酮糖中的应用 | |
| CN111471667B (zh) | 壳聚糖酶Csn-PT及其应用 | |
| CN109609485A (zh) | 一种甲壳素脱乙酰酶及其应用 | |
| CN116478973A (zh) | 梅片树倍半萜合酶CbTPS6及其相关生物材料与应用 | |
| CN113817758A (zh) | 编码贝莱斯芽孢杆菌的壳聚糖酶基因、壳聚糖酶及其制备方法和应用 | |
| CN114317494B (zh) | 一种α-L-鼠李糖苷酶突变体及其应用 | |
| CN111549007A (zh) | 一种转氨酶tsta、制备方法和应用 | |
| CN120230734B (zh) | 蔗糖磷酸化酶突变体及其在合成2-O-α-D-吡喃葡萄糖基-L-抗坏血酸中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |