新型短肽类HIV-1融合抑制剂的研究进展  

The research process of novel short peptide-based HIV-1 fusion inhibitors

作　　者：黄妍 赵岩 嘎鲁 梁国栋 霍彩霞 HUANG Yan;ZHAO Yan;GA Lu;LIANG Guodong;HUO Caixia(Key Laboratory for Candidate Drug Design and Screening Based on Chemical Biology,School of Pharmacy,Inner Mongolia Medical University,Hohhot 010110,China)

机构地区：[1]内蒙古医科大学药学院,基于化学生物学的候选药物设计与筛选重点实验室,内蒙古自治区呼和浩特010110

出　　处：《中国药物化学杂志》2024年第5期409-420,共12页Chinese Journal of Medicinal Chemistry

基　　金：内蒙古自治区自然科学基金项目(2023LHMS08045);内蒙古医科大学青年项目(YKD2023QN053);内蒙古医科大学学科建设项目(YKD2024XK006);内蒙古医科大学药学院博士启动基金项目(YXY2023BSJJ701)。

摘　　要：艾滋病是由1型人类免疫缺陷病毒(HIV-1)引起的危害性极大的传染病。T20是首个获批上市的多肽类HIV-1融合抑制剂,在艾滋病的临床治疗中发挥着重要作用。然而,T20在临床应用中存在耐药、体内代谢稳定性差以及价格昂贵等问题,因此,设计能够解决T20临床应用缺陷的新型肽类融合抑制剂成为研究热点。短肽合成成本低,通过修饰能够提高抗病毒活性,改善代谢稳定性,有望解决当前肽类融合抑制剂存在的问题。本文作者对E-K盐桥改造、订书肽修饰、小分子-多肽缀合物修饰、多肽N端“M-T hook”结构优化、多肽C端“IDL tail”结构优化等短肽类HIV-1融合抑制剂的研发策略进行综述,以期为新型抗HIV-1药物的研发提供有价值的借鉴和参考。Acquired immunodeficiency syndrome(AIDS)is a devastating infectious disease caused by the human immunodeficiency virus type 1(HIV-1).T20 is the first approved fusion inhibitor against HIV-1,and plays an important role in AIDS treatment.However,T20 has some problems such as drug resistance,poor metabolic stability in vivo and high cost in clinical use.Therefore,the design of novel peptide fusion inhibitors which can solve the defects of T20 has become a research focus.Short peptides are low-cost to produce and can be modified to improve bioavailability and anti-drug resistance,which is expected to solve the current dilemma of fusion inhibitors.In this paper,the research for short peptide-based fusion inhibitors against HIV-1,such as E-K salt bridge modification,stapled peptide modification,small molecule-peptide conjugation modification,N terminal“M-T hook”of peptide structure optimization and C terminal“IDL tail”of peptide structure optimization were summarized,looking forward to provide valuable reference for the research and development of new anti-HIV-1 drugs.

关 键 词：人类免疫缺陷病毒 获得性免疫缺陷综合征 融合抑制剂 短肽 

分 类 号：R914[医药卫生—药物化学]