摘要
本研究以血管紧张素I转化酶(angiotensin converting enzyme,ACE)抑制肽PHP1和PHP2为研究母肽,通过替换氨基酸残基改变目标多肽的疏水性、带电性等因素,利用生物信息学工具评估多肽潜在的生物活性,设计了19个多肽类似物。采用多肽固相合成法合成目的多肽类似物,并进行体外生物活性检测。结果显示多肽类似物均具有较高的ACE抑制活性,其中,PHP1A-6(IC_(50)=3.87μmol/L)、PHP2A-3(IC_(50)=3.33μmol/L)、PHP2A-4(IC_(50)=2.86μmol/L)和PHP2A-7(IC_(50)=4.58μmol/L)的ACE抑制活性最高,较母肽有显著提高(P<0.05),PHP1A-3、PHP1A-4、PHP1A-7、PHP2A-1和PHP2A-10具有同母肽相当的抑制活性,IC_(50)<10μmol/L。绝大部分多肽类似物的α-葡萄糖苷酶抑制活性与母肽相比均有明显提高,PHP1A-3(IC_(50)=3.09μmol/L)、PHP1A-7(IC_(50)=9.51μmol/L)、PHP2A-6(IC_(50)=5.58μmol/L)、PHP2A-11(IC_(50)=2.35μmol/L)和PHP2A-12(IC_(50)=3.98μmol/L)的活性最高。其中,PHP1A-3和PHP1A-7具备较强的ACE抑制和α-葡萄糖苷酶抑制双重活性。含Cys的多肽类似物在1 mg/mL浓度下,ABTS+·清除率均在85%以上,具备潜在的抗氧化活性。分子对接研究了ACE抑制肽与ACE的构效关系,表明抑制肽可以与ACE的氨基酸残基产生多个稳定的氢键、疏水相互作用、π-π堆积及盐桥,增加了对ACE的抑制作用。
In this study,using angiotensin converting enzyme(ACE)inhibitory peptides PHP1 and PHP2 as the parent peptides,the hydrophobicity and electrical properties of target polypeptides were altered by substituting amino acid residues.In addition,the potential bioactivity of these polypeptides was assessed using bioinformatics tools.Following this analysis,19 polypeptide analogues were designed and synthesized using solid-phase synthesis,and their bioactivities were detected in vitro.The results revealed that the polypeptide analogues showed relatively high ACE inhibitory activities,PHP1A-6(IC_(50)=3.87μmol/L),PHP2A-3(IC_(50)=3.33μmol/L),PHP2A-4(IC_(50)=2.86μmol/L),and PHP2A-7(IC_(50)=4.58μmol/L)exhibited the highest ACE inhibitory activity levels,significantly higher than the parent peptides(P<0.05).PHP1A-3,PHP1A-4,PHP1A-7,PHP2A-1 and PHP2A-10 displayed equal levels of inhibitory activity in comparison to the parent peptides(IC_(50)<10μmol/L).Compared with the parent peptides,theα-glucosidase inhibitory activity levels demonstrated by most of the polypeptide analogues were significantly enhanced,PHP1A-3(IC_(50)=3.09μmol/L),PHP1A-7(IC_(50)=9.51μmol/L),PHP2A-6(IC_(50)=5.58μmol/L),PHP2A-11(IC_(50)=2.35μmol/L),and PHP2A-12(IC_(50)=3.98μmol/L)exhibited the highest activities.Additionally,PHP1A-3 and PHP1A-7 displayed relatively strong inhibitory activity against both ACE andα-glucosidase.At concentrations of 1 mg/mL,the polypeptides containing Cys displayed an ABTS+·scavenging rate of higher than 85%,demonstrating a potential antioxidant activity.The structure-activity relationship between the ACE inhibitory peptides and ACE were explored using molecular docking.The results reflected that inhibitory peptides produced multiple stable hydrogen bonds,hydrophobic interactions,π-πstacking interactions,and salt bridges with ACE amino acid residues,thereby improving the inhibitory effects exerted on ACE.
作者
周佳琪
马春燕
李晓晖
ZHOU Jiaqi;MA Chunyan;LI Xiaohui(College of Bioengineering,Dalian University of Technology,Dalian 116024,China;College of Chemical Engineering,Dalian University of Technology,Dalian 116024,China)
出处
《食品工业科技》
CAS
北大核心
2022年第23期26-34,共9页
Science and Technology of Food Industry
关键词
多肽固相合成
新型
ACE
抑制肽类似物
生物活性
分子对接
solid-phase peptide synthesis
novel ACE inhibitory peptide analogue
biological activity
molecular docking
