CN113480605A - 一种牦牛乳酪蛋白dpp-iv抑制肽及其筛选方法 - Google Patents
一种牦牛乳酪蛋白dpp-iv抑制肽及其筛选方法 Download PDFInfo
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- CN113480605A CN113480605A CN202110852138.4A CN202110852138A CN113480605A CN 113480605 A CN113480605 A CN 113480605A CN 202110852138 A CN202110852138 A CN 202110852138A CN 113480605 A CN113480605 A CN 113480605A
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- dpp
- inhibitory peptide
- casein
- yak milk
- milk casein
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Abstract
本发明公开了一种牦牛乳酪蛋白DPP‑IV抑制肽及其筛选方法，涉及医药技术领域。本发明牦牛乳酪蛋白DPP‑IV抑制肽的氨基酸序列包括LPVPQK(β‑CN，f221‑226)，对DPP‑IV的作用模式为竞争性抑制，DPP‑IV抑制率为69.56±1.86％，IC50值为4.38μM。抑制肽LPVPQK与DPP‑IV分子活性位点中在Glu205(A)、Ser630(A)和Glu206(A)三个位置形成氢键，且与Tyr666(A)、Phe357(A)、Tyr547(A)和Tyr662(A)四个位置形成疏水相互作用。本发明筛选方法开创性地将凝乳酶与木瓜蛋白酶联合降解牦牛乳酪蛋白，用于生产高活性DPP‑IV抑制肽，所得抑制肽LPVPQK对DPP‑IV的抑制率高，对糖尿病患者而言降低血糖安全可靠。
Description
技术领域
本发明涉及医药技术领域，更具体的说是涉及一种牦牛乳酪蛋白DPP-IV抑制肽及其筛选方法。
背景技术
DPP-IV(二肽基肽酶-IV)抑制剂是糖尿病患者控制血糖的常用药物，通过减少DPP-IV对GLP-1(胰高血糖素样肽-1)的降解降低血糖水平，含有Xaa-Pro类似结构，可竞争性地结合DPP-IV的活化部位，具有化学合成类药物的副作用。
很多食源性多肽也含有Xaa-Pro类似结构，可起到DPP-IV抑制效果。DPP-IV抑制肽的结构特点一般有以下几个：N-末端含疏水性氨基酸(Trp/Leu/Ile/Phe)、2位上有Pro/Ala/Thr/His/Gly和/或C-末端有Trp/Phe/Pro，脯氨酸含量高的蛋白质产生DPP-IV抑制肽的潜力更大。
因此，开发食源性DPP-IV抑制剂是本领域技术人员亟需解决的技术问题。
发明内容
有鉴于此，本发明提供了一种牦牛乳酪蛋白DPP-IV抑制肽及其筛选方法。本发明牦牛乳酪蛋白DPP-IV抑制肽具有良好的DPP-IV抑制率，对糖尿病患者降低血糖安全可靠。
为了实现上述目的，本发明采用如下技术方案：
一种牦牛乳酪蛋白DPP-IV抑制肽，所述抑制肽的氨基酸序列包括LPVPQK(β-CN，f221-226)，SEQ ID NO：1。
作为本发明优选的技术方案，所述牦牛乳酪蛋白DPP-IV抑制肽与DPP-IV分子活性位点中在Glu205(A)、Ser630(A)和Glu206(A)三个位置形成氢键，且与Tyr666(A)、Phe357(A)、Tyr547(A)和Tyr662(A)四个位置形成疏水相互作用。
以上技术方案的有益效果：牦牛乳酪蛋白DPP-IV抑制肽LPVPQK结合于DPP-IV的活性位点，对DPP-IV产生竞争性抑制作用，因而可以缓解DPP-IV对胰高血糖素样肽-1的降解作用，实现降血糖的效果。
本发明的另一目的是，提供上述牦牛乳酪蛋白DPP-IV抑制肽的筛选方法，包括以下步骤：
(1)牦牛乳酪蛋白酶解处理：将牦牛乳酪蛋白润湿后添加无水碳酸钠搅拌至完全溶解，调节pH值，设置三个酶解组进行酶解处理，酶解后的产物经沸水浴灭酶、冰水浴冷却后离心，将上清液冻干，得酶解产物冻干粉；
所述三个酶解组分别是凝乳酶酶解组、木瓜蛋白酶酶解组、凝乳酶预处理酶解组；
(2)牦牛乳酪蛋白酶解产物超滤分离：将酶解产物冻干粉配制成多肽溶液，用过滤膜去除大分子杂质，再用带有超滤膜的超滤离心管对所述多肽溶液进行离心分离，收集＜3kDa滤液；
(3)超滤分离产物的LC-MS分析：将步骤(2)所得＜3kDa滤液上样LC-MS分析，并利用蛋白质谱分析软件进行氨基酸序列分析；
(4)潜能DPP-IV抑制肽的识别：对步骤(3)所得氨基酸序列分析结果，将凝乳酶预处理酶解组的氨基酸序列中与凝乳酶酶解组相同的氨基酸序列或与木瓜蛋白酶酶解组相同的氨基酸序列排除，再将水溶性差的片段和已公开的DPP-IV抑制肽片段排除，剩余的氨基酸序列中与DPP-IV抑制肽结构相似的确定为潜能DPP-IV抑制肽；
(5)潜能DPP-IV抑制肽活性鉴定。
有益效果：我国牦牛乳资源丰富，牦牛乳蛋白质含量高达5.24％，而其中的80％为酪蛋白。溶液中，牦牛乳酪蛋白大多以胶束状态存在，胶束表面主要由κ-酪蛋白覆盖。本发明将凝乳酶和木瓜蛋白酶用于降解牦牛乳酪蛋白，水解产物表现出良好的DPP-IV抑制活性。木瓜蛋白酶具有较宽的底物特异性，作用于蛋白质中L-精氨酸、L-赖氨酸、甘氨酸和L-瓜木瓜蛋白酶氨酸残基羧基参与形成的肽键。此酶属内肽酶，能切开全蛋蛋白质分子内部肽链-CO-NH-生成分子量较小的多肽类。凝乳酶是一种最早在未断奶的小牛胃中发现的天门冬氨酸蛋白酶，可专一地切割乳中κ-酪蛋白的Phe105-Met106之间的肽键，破坏酪蛋白胶束使牛奶凝结，凝乳酶的凝乳能力及蛋白水解能力使其成为干酪生产中形成质构和特殊风味的关键性酶，被广泛地应用于奶酪和酸奶的制作。本发明开创性地将凝乳酶与木瓜蛋白酶联合降解牦牛乳酪蛋白，用于生产高活性DPP-IV抑制肽，所得抑制肽LPVPQK对DPP-IV的抑制率为69.56±1.86％，IC50值为4.38μM，对糖尿病患者而言降低血糖安全可靠。
作为本发明优选的技术方案，步骤(1)所述三个酶解组酶解处理条件分别为：
凝乳酶酶解组：酪蛋白用凝乳酶酶解0.5h，凝乳酶添加量为每克酪蛋白添加120U凝乳酶；
木瓜蛋白酶酶解组：酪蛋白用木瓜蛋白酶酶解2h，木瓜蛋白酶的添加量为每克酪蛋白添加3000U木瓜蛋白酶；
凝乳酶预处理酶解组：酪蛋白先用凝乳酶酶解0.5h，再用木瓜蛋白酶酶解2h，凝乳酶添加量为每克酪蛋白添加120U凝乳酶，木瓜蛋白酶的添加量为每克酪蛋白添加3000U木瓜蛋白酶；
且，三个酶解组酶解处理前均将酪蛋白在37℃预热0.5h。
作为本发明优选的技术方案，步骤(1)所述三个酶解组酶解温度均为37℃，且酶解过程中用1mol/L HCl或1mol/LNaOH稳定pH值在6.0。
作为本发明优选的技术方案，步骤(1)所述离心条件为4℃下，8000rpm离心15min，且离心后的上清液调节pH至8.0后再行冻干。
作为本发明优选的技术方案，步骤(1)所述无水碳酸钠添加量为酪蛋白质量的5％；沸水浴灭酶10min。
作为本发明优选的技术方案，步骤(2)所述多肽溶液的浓度为20mg/ml。
作为本发明优选的技术方案，步骤(2)超滤离心时，依次用含10kDa和3kDa超滤膜的超滤离心管离心，离心参数为4℃下，6000rpm离心50min。
作为本发明优选的技术方案，除去大分子杂质所用滤膜孔径为0.22μm。
作为本发明优选的技术方案，步骤(3)LC-MS参数如下：
色谱条件：
色谱柱规格：100mm×4.6mm，5μm。柱温：40℃。进样量：5.0μL。流动相：A，0.1％甲酸水；B，乙腈。梯度洗脱条件见表1。
表1梯度洗脱条件
质谱条件：
离子源：HESI；鞘气速率：40mL/min；辅助气速率：10mL/min；喷雾电压：正离子3.0kV；毛细管温度：320℃；辅助气温度：300℃；S-lens：50％。扫描模式：Fullms/dd-ms2top10。扫描范围：一级扫描：分辨率70000，范围200～1600m/z；二级扫描：分辨率17500，起始离子50m/z。多肽匹配：preferred；碰撞电压：NCE27。
作为本发明优选的技术方案，滤液上LC-MS分析前需要过0.22μm的微孔滤膜。所述蛋白质谱分析软件分析软件为MaxQuant1.5.2.8。
作为本发明优选的技术方案，所述(4)潜能DPP-IV抑制肽识别步骤仅对10肽及以下片段进行分析。
所述水溶性差的片段用PROTEIN CULATOR v3.4进行排除。
经由上述的技术方案可知，与现有技术相比，本发明公开提供了一种牦牛乳酪蛋白DPP-IV抑制肽及其筛选方法。本发明牦牛乳酪蛋白DPP-IV抑制肽的氨基酸序列包括LPVPQK(β-CN，f221-226)，与DPP-IV的作用模式为竞争性抑制，对DPP-IV的抑制率为69.56±1.86％，IC50值为4.38μM。抑制肽LPVPQK与DPP-IV分子活性位点中在Glu205(A)、Ser630(A)和Glu206(A)三个位置形成氢键，且与Tyr666(A)、Phe357(A)、Tyr547(A)和Tyr662(A)四个位置形成疏水相互作用。本发明筛选方法开创性地将凝乳酶与木瓜蛋白酶联合降解牦牛乳酪蛋白，用于生产高活性DPP-IV抑制肽，所得抑制肽LPVPQK对DPP-IV的抑制率高，对糖尿病患者而言降低血糖安全可靠。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据提供的附图获得其他的附图。
图1附图为本发明实施例1凝乳酶预处理酶解组的特异性多肽片段谱图；其中A来源为αs1-酪蛋白，B来源为αs2-酪蛋白，C来源为β-酪蛋白，D来源为κ-酪蛋白；
图2附图为本发明实施例2潜能抑制肽LPVPQK分子结构图；
图3附图为本发明实施例3抑制肽LPVPQK与DPP-IV分子对接结果三维图；
图4附图为本发明实施例3抑制肽LPVPQK与DPP-IV分子相互作用分析图。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
本发明实施例公开了牦牛乳酪蛋白DPP-IV抑制肽及其筛选方法，所用试剂均为市售可得，所用方法如无特殊提交均为常规方法，在此不再一一赘述。
实施例1
(1)牦牛乳酪蛋白酶解处理：将牦牛乳酪蛋白用蒸馏水润湿后添加5％wt无水碳酸钠搅拌3h，完全溶解，调节pH值6.0，设置三个酶解组进行酶解处理，酶解后的产物经沸水浴10min灭酶、冰水浴冷却后离心(4℃，8000rpm离心15min)，将上清液调节pH至8.0后冻干，得酶解产物冻干粉，保存于-20℃冰箱；
其中，三个酶解组分别是凝乳酶酶解组、木瓜蛋白酶酶解组、凝乳酶预处理酶解组；
酶解处理方法分别为：
凝乳酶酶解组：酪蛋白用凝乳酶酶解0.5h，凝乳酶添加量为每克酪蛋白添加120U凝乳酶；
木瓜蛋白酶酶解组：酪蛋白用木瓜蛋白酶酶解2h，木瓜蛋白酶的添加量为每克酪蛋白添加3000U木瓜蛋白酶；
凝乳酶预处理酶解组：酪蛋白先用凝乳酶酶解0.5h，再用木瓜蛋白酶酶解2h，凝乳酶添加量为每克酪蛋白添加120U凝乳酶，木瓜蛋白酶的添加量为每克酪蛋白添加3000U木瓜蛋白酶；
且，三个酶解组酶解处理前均将酪蛋白在37℃预热0.5h，三个酶解组酶解温度均为37℃，且酶解过程中用1mol/L HCl或1mol/LNaOH稳定pH值在6.0。
(2)牦牛乳酪蛋白酶解产物超滤分离：将酶解产物冻干粉用超纯水配制成20mg/ml的多肽溶液，用0.22μm过滤膜去除大分子杂质，再依次用带有截留分子量10kDa、3kDa超滤膜的超滤离心管对多肽溶液进行离心分离，4℃下，6000rpm离心50min，收集＜3kDa滤液，储存于-20℃冰箱；
(3)超滤分离产物的LC-MS分析：将步骤(2)所得＜3kDa滤液经0.22μm微孔滤膜上样LC-MS进行分析，并利用蛋白质谱分析软件MaxQuant 1.5.2.8进行氨基酸序列分析；结果显示凝乳酶酶解组检测到270条多肽，木瓜蛋白酶酶解组检测到908条多肽，凝乳酶预处理酶解组检测到807条多肽。
其中色谱条件如下：
色谱柱规格：100mm×4.6mm，5μm。柱温：40℃。进样量：5.0μL。流动相：A，0.1％甲酸水；B，乙腈。梯度洗脱条件见表1。
表1梯度洗脱条件
质谱条件如下：
离子源：HESI；鞘气速率：40mL/min；辅助气速率：10mL/min；喷雾电压：正离子3.0kV；毛细管温度：320℃；辅助气温度：300℃；S-lens：50％。扫描模式：Fullms/dd-ms2top10。扫描范围：一级扫描：分辨率70000，范围200～1600m/z；二级扫描：分辨率17500，起始离子50m/z。多肽匹配：preferred；碰撞电压：NCE27。
(4)潜能DPP-IV抑制肽的识别：对步骤(3)所得氨基酸序列分析结果，将凝乳酶预处理酶解组的氨基酸序列中与凝乳酶酶解组相同的氨基酸序列或与木瓜蛋白酶酶解组相同的氨基酸序列排除，得到凝乳酶预处理酶解组的特异性多肽片段(如附图1所示)，牛乳酪蛋白存在αs1-酪蛋白、αs2-酪蛋白、β-酪蛋白、κ-酪蛋白四种结构，其氨基酸序列分别如SEQID NO：2-5所示；因生物活性肽数据库中大部分DPP-IV抑制肽的氨基酸数量小于10，故仅对其中10肽以下的片段进行分析，利用PROTEIN CALCULATOR v3.4(http://protcalc.sourceforge.net/)排除水溶性差的多肽片段，查找生物活性肽数据库查找和文献数据库将已公开的DPP-IV抑制肽片段排除，剩余的氨基酸序列中与DPP-IV抑制肽结构相似的确定为潜能DPP-IV抑制肽；
目前研究发现的DPP-IV抑制肽一般有以下结构特点：N-末端含疏水性氨基酸(Trp/Leu/Ile/Phe)、2位上有Pro/Ala/Thr/His/Gly和/或C-末端有Trp/Phe/Pro。
本实施例获得一条具有DPP-IV抑制潜能的多肽LPVPQK(β-CN，f221-226)，SEQ IDNO：1。
(5)潜能DPP-IV抑制肽活性鉴定。
实施例2
潜能抑制肽肽LPVPQK的活性鉴定
潜能抑制肽LPVPQK委托强耀生物科技有限公司合成(合成量10mg)。
(1)对潜能抑制肽LPVPQK进行DPP-IV抑制率测定，以抑制肽浓度的对数值为横坐标、DPP-IV抑制率为纵坐标，利用回归分析方法计算得出合成肽对DPP-IV的IC50值。
DPP-IV抑制率测定方法：
以Gly-Pro-pNA为底物，利用发色底物法测定潜能抑制肽LPVPQK的抑制活性。测定样品为合成LPVPQK多肽粉，以8mg/mL溶解于0.1mol/L Tris-HCl缓冲液(pH8.0)。在酶标板中，加入25μL待测样品溶液与25μL底物(浓度6.4mmol/L)，混合后在37℃下孵育10min。加入50μL DPP-IV酶液(酶活力32U/L)，混匀后在37℃下精确孵育60min，孵育结束后立即加入100μL 1mol/L醋酸-醋酸钠(pH 4.0)缓冲液终止反应，在405nm下测吸光度值(A)。以相同体积的0.1mol/L Tris-HCl缓冲液(pH8.0)作为阴性对照组反应物质进行测定。以抑制肽浓度的对数值为横坐标、DPP-IV抑制率为纵坐标，利用回归分析方法计算得出合成肽对DPP-IV的IC50值。
DPP-IV抑制率计算公式如下：
潜能抑制肽LPVPQK DPP-IV抑制率和IC50计算：
DPP-IV抑制率为69.56±1.86％，IC50为4.38μM。
采用PyMOl(2.3.0)绘制多肽(如附图2所示)，然后导入Chembio 3D进行能量最小化，导入AutoDock Tools(v1.5.6)，按照软件默认参数加氢、计算电荷、分配电荷、设置可旋转键后保存为“pdbqt”格式。
潜能抑制肽LPVPQK的DPP-IV抑制率为69.56±1.86％，IC50为4.38μM，确定为DPP-IV抑制肽。据β-酪蛋白在牦牛乳酪蛋白中的含量以及牦牛乳酪蛋白的纯度计算可得，该DPP-IV抑制肽在牦牛乳酪蛋白中的理论产量为295.2(mg/g酪蛋白)。
实施例3
DPP-IV抑制肽LPVPQK作用模式研究
DPP-IV结构从Protein Data Bank(http://www.rcsb.org/)下载得到(PDB ID:2ONC)。将蛋白导入PyMOL(2.3.0)去除原始配体和水分子，然后将蛋白导入AutoDock Tools(v1.5.6)进行加氢、计算电荷、分配电荷、指定原子类型并保存为“pdbqt”格式。DPP-IV活性口袋的坐标设置为：centerx＝-44.532，centery＝-19.908，center z＝18.125；size x＝90；size y＝90；size z＝80，其它参数默认设置。利用PyMOL(2.3.0)和Ligplot(2.2.4)进行对接结果的相互作用模式分析。
DPP-IV抑制肽LPVPQK与DPP-IV分子结合产生的最稳定构象(如附图3所示)，该构象的结合能为-7.8kcal/mol。抑制肽LPVPQK与DPP-IV分子的残基Glu205(A)、Ser630(A)、Tyr752(A)、Gly741(A)、Glu206(A)共形成八个氢键，氢键长度分别为
2.89、
除此之外，LPVPQK与DPP-IV分子的Tyr666(A)、Trp627(A)、Tyr48(A)、Asp545(A)、Phe357(A)、His748(A)、Trp629(A)、Lys554(A)、Tyr547(A)和Tyr662(A)之间均存在疏水作用(如附图4所示)，故二者之间也存在较强的疏水相互作用。根据以上实验结果可知，抑制肽LPVPQK与DPP-IV分子活性位点中的Glu205(A)、Ser630(A)和Glu206(A)三个位置形成氢键，且与Tyr666(A)、Phe357(A)、Tyr547(A)和Tyr662(A)四个位置形成疏水相互作用，故该分子结合在DPP-IV的活性位点，所以抑制肽LPVPQK对DPP-IV的作用模式为竞争性抑制。
本说明书中各个实施例采用递进的方式描述，每个实施例重点说明的都是与其他实施例的不同之处，各个实施例之间相同相似部分互相参见即可。
对所公开的实施例的上述说明，使本领域专业技术人员能够实现或使用本发明。对这些实施例的多种修改对本领域的专业技术人员来说将是显而易见的，本文中所定义的一般原理可以在不脱离本发明的精神或范围的情况下，在其它实施例中实现。因此，本发明将不会被限制于本文所示的这些实施例，而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。
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Claims (9)
1.一种牦牛乳酪蛋白DPP-IV抑制肽，其特征在于，所述抑制肽的氨基酸序列包括LPVPQK。
2.根据权利要求1所述的牦牛乳酪蛋白DPP-IV抑制肽，其特征在于，所述DPP-IV抑制肽与DPP-IV分子活性位点中在Glu205(A)、Ser630(A)和Glu206(A)三个位置形成氢键，且与Tyr666(A)、Phe357(A)、Tyr547(A)和Tyr662(A)四个位置形成疏水相互作用。
3.一种牦牛乳酪蛋白DPP-IV抑制肽的筛选方法，其特征在于，包括以下步骤：
(1)牦牛乳酪蛋白酶解处理：将牦牛乳酪蛋白润湿后添加无水碳酸钠搅拌至完全溶解，调节pH值，设置三个酶解组进行酶解处理，酶解后的产物经沸水浴灭酶、冰水浴冷却后离心，将上清液冻干，得酶解产物冻干粉；
所述三个酶解组分别是凝乳酶酶解组、木瓜蛋白酶酶解组、凝乳酶预处理酶解组；
(2)牦牛乳酪蛋白酶解产物超滤分离：将酶解产物冻干粉配制成多肽溶液，用过滤膜去除大分子杂质，再用带有超滤膜的超滤离心管对所述多肽溶液进行离心分离，收集＜3kDa滤液；
(3)超滤分离产物的LC-MS分析：将步骤(2)所得＜3kDa滤液上样LC-MS分析，并利用蛋白质谱分析软件进行氨基酸序列分析；
(4)潜能DPP-IV抑制肽的识别：对步骤(3)所得氨基酸序列分析结果，将凝乳酶预处理酶解组的氨基酸序列中与凝乳酶酶解组相同的氨基酸序列或与木瓜蛋白酶酶解组相同的氨基酸序列排除，再将水溶性差的片段和已公开的DPP-IV抑制肽片段排除，剩余的氨基酸序列中与DPP-IV抑制肽结构相似的确定为潜能DPP-IV抑制肽；
(5)潜能DPP-IV抑制肽活性鉴定。
4.根据权利要求3所述牦牛乳酪蛋白DPP-IV抑制肽的筛选方法，其特征在于，步骤(1)所述三个酶解组酶解处理条件分别为：
凝乳酶酶解组：酪蛋白用凝乳酶酶解0.5h，凝乳酶添加量为每克酪蛋白添加120U凝乳酶；
木瓜蛋白酶酶解组：酪蛋白用木瓜蛋白酶酶解2h，木瓜蛋白酶的添加量为每克酪蛋白添加3000U木瓜蛋白酶；
凝乳酶预处理酶解组：酪蛋白先用凝乳酶酶解0.5h，再用木瓜蛋白酶酶解2h，凝乳酶添加量为每克酪蛋白添加120U凝乳酶，木瓜蛋白酶的添加量为每克酪蛋白添加3000U木瓜蛋白酶；
且，三个酶解组酶解处理前均将酪蛋白在37℃预热0.5h。
5.根据权利要求3所述牦牛乳酪蛋白DPP-IV抑制肽的筛选方法，其特征在于，步骤(1)所述三个酶解组酶解温度均为37℃，且酶解过程中用1mol/L HCl或1mol/LNaOH稳定pH值在6.0。
6.根据权利要求3所述牦牛乳酪蛋白DPP-IV抑制肽的筛选方法，其特征在于，步骤(1)所述离心条件为4℃下，8000rpm离心15min，且离心后的上清液调节pH至8.0后再行冻干。
7.根据权利要求3所述牦牛乳酪蛋白DPP-IV抑制肽的筛选方法，其特征在于，步骤(2)所述多肽溶液的浓度为20mg/ml。
8.根据权利要求3所述牦牛乳酪蛋白DPP-IV抑制肽的筛选方法，其特征在于，步骤(2)超滤离心时，依次用含10kDa和3kDa超滤膜的超滤离心管离心，离心参数为4℃下，6000rpm离心50min。
9.根据权利要求3所述牦牛乳酪蛋白DPP-IV抑制肽的筛选方法，其特征在于，所述(4)潜能DPP-IV抑制肽识别步骤仅对10肽及以下片段进行分析。
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| CN114686551A (zh) * | 2022-03-16 | 2022-07-01 | 江南大学 | 一种豌豆蛋白源dpp-iv抑制肽及其筛选方法 |
| CN114686551B (zh) * | 2022-03-16 | 2023-08-08 | 江南大学 | 一种豌豆蛋白源dpp-iv抑制肽及其筛选方法 |
| CN117384270A (zh) * | 2023-10-13 | 2024-01-12 | 华南理工大学 | 一种酪蛋白源dpp-iv抑制六肽及其制备方法与应用 |
| CN119859168A (zh) * | 2025-03-21 | 2025-04-22 | 中国海洋大学 | 一种兼具ace和dpp-iv抑制活性的双功能活性肽及其制备方法与应用 |
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