环肽合成策略及其在新药研发中的应用研究进展  

Research progress of cyclic peptide synthesis strategy and its application in new drug development

作　　者：苏思佳 卜庆伟 盛春泉 武善超 SU Si-jia;BU Qing-wei;SHENG Chun-quan;WU Shan-chao(School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China;Second Military Medical University,Shanghai 200433,China)

机构地区：[1]温州医科大学药学院,浙江温州325035 [2]中国人民解放军海军军医大学,上海200433

出　　处：《药学学报》2023年第3期629-638,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(22077138,81725020);上海市青年科技启明星计划(22QA1411300)。

摘　　要：蛋白-蛋白相互作用(protein-protein interaction,PPI)在生命调控过程中扮演着重要角色,多肽因具有更高的亲和力和特异性在参与PPI表面相互作用中发挥着重要作用。然而,多肽存在易被蛋白酶水解、膜通透性差等缺陷。相比于直链多肽,环肽因其良好的生物相容性和化学多样性能够很好地克服以上缺陷,在新药研发中发挥着重要作用,因而,发展高效的环肽构建方法成为了多肽药物研究的前沿问题。近年来,环肽合成策略及其在新药研发中的应用方面取得了一系列新进展,为研发环肽类药物提供了有力的技术工具。本文将从合成策略、性质改善、生物活性及前景展望四方面综述环肽合成策略及其在新药研发中的应用研究进展。Protein-protein interaction(PPI)plays an important role in the regulation of life.Most of the PPI interfaces are large and discontinuous,and it is difficult for small molecules to specifically bind to them.Peptides are critical in PPI surface interactions due to their higher affinity and specificity.However,peptides have some defects such as easy hydrolysis by protease and poor membrane permeability.Due to good biocompatibility and chemical diversity,cyclic peptides play an important role in drug discovery.Therefore,the development of efficient cyclic peptide construction methods has become a frontier issue in peptide drug research.In recent years,a series of new progresses have been made in the synthesis strategy and the application of cyclic peptides,providing powerful technical tools for the research and development of cyclic peptide drugs.In this review,the synthesis strategies of cyclic peptides and their application will be reviewed from four aspects:synthesis strategies,property improvement,biological activity and prospect.

关 键 词：多肽 环肽 合成策略 性质改善 生物活性 

分 类 号：R914[医药卫生—药物化学]