三种Mastoparan胡蜂多肽的抗菌功能和分子优化研究  

Study on the Antibacterial Function and Molecular Optimization of Three Wasp Mastoparan Peptides

作　　者：叶祥东 周海梅 孙芳 覃陈虎 陈宗运 罗旭东 YE Xiang-dong;ZHOU Hai-mei;SUN Fang;QIN Chen-hu;CHEN Zong-yun;LUO Xu-dong(Department of Biochemistry and Molecular Biology,College of Basic Medicine;Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Hubei University of Medicine,Shiyan,Hubei 442000,China)

机构地区：[1]湖北医药学院基础医学院生物化学教研室 [2]武当特色中药研究湖北省重点实验室,湖北十堰442000

出　　处：《湖北医药学院学报》2023年第5期469-474,共6页Journal of Hubei University of Medicine

基　　金：国家自然科学基金青年项目(82204407);湖北省卫健委科研项目-面上项目(WJ2021M060);湖北医药学院人才启动金项目(2020QDJZR011);武当特色中药研究湖北省重点实验室开放课题(WDCM2023011)。

摘　　要：目的:探究Protopolybia exigua胡蜂毒液来源Mastoparan家族蜂毒肽Protopolybia-MPⅠ、-MPⅡ和-MPⅢ的结构特征与抗菌功能并进行分子优化。方法:结合分子模拟和圆二色谱法分析Protopolybia-MPⅠ、-MPⅡ和-MPⅢ的结构特征,采用MIC方法评价Protopolybia-MPⅠ、-MPⅡ和-MPⅢ的抗菌活性;基于Protopolybia-MPⅠ与-MPⅢ的序列与活性差异设计突变体并进行抗菌活性评价。结果:Protopolybia-MPⅠ、-MPⅡ和-MPⅢ均具有典型的α-螺旋构象;Protopolybia-MPⅢ对金黄色葡萄球菌和鲍曼不动杆菌具有显著的抗菌活性;通过设计突变体发现Protopolybia-MPⅢ-3、-6与-12的抗菌活性明显改善。结论:本研究为临床新型肽类抗菌药物的研发提供了先导分子,并丰富了对Mastoparan家族蜂毒肽的认识。Objective To investigate the structural characteristics and antimicrobial functions of three Mastoparan family peptides(Protopolybia-MPⅠ,-MPⅡ and-MPⅢ)from Protopolybia exigua wasp venom and to optimize molecular prop⁃erties.Methods The structural characteristics of Protopolybia-MPⅠ,-MPⅡand-MPⅢ were analyzed by molecular sim⁃ulation and circular binary chromatography,and the antibacterial activities of Protopolybia-MPⅠ,-MPⅡ and-MPⅢ were evaluated by MIC method.The mutants were designed based on the sequence and activity differences between Protopo⁃lybia-MPⅠand-MPⅢ,and the antibacterial activity was evaluated.Results Protopolybia-MPⅠ,-MPⅡand-MPⅢ all had typical α-helical conformation.Protopolybia-MPⅢ had significant antibacterial activity against S.aureus and A.baumannii.By designing mutants,it was found that the antibacterial activity of Protopolybia-MP Ⅲ-3,-6,and-12 was significantly improved.Conclusion This study provides a leading molecule for the research and development of novel anti⁃microbial drugs in clinical practice,and enriches the understanding of Mastoparan family peptides of wasp venom.

关 键 词：蜂毒肽 Mastoparan家族多肽 Protopolybia-MPⅢ 抗菌活性 分子优化 

分 类 号：R91[医药卫生—药学]