用作HIV-1融合抑制剂的多肽及其类似物  

The peptides and peptidomimetics: HIV-1 fusion inhibitors

作　　者：贾启燕[1] 蔡利锋[1] 刘克良[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国科学：化学》2013年第8期984-994,共11页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(81202390)资助

摘　　要：HIV-1通过其包膜糖蛋白跨膜亚基gp41介导的病毒-细胞膜融合进入和感染靶细胞.HIV-1融合抑制剂以gp41为靶点,通过阻断病毒与宿主细胞膜的融合,在感染的初始环节切断HIV-1的复制周期.2003年,首个多肽类融合抑制剂T-20获美国食品药物管理局(FDA)批准上市,但其易被体内蛋白酶降解、临床剂量大、耐受性差,且耐药性HIV-1毒株也很快出现.针对这些缺点,近年来在融合抑制剂的作用机制研究和新融合抑制剂的研发等方面取得了重要进展.以gp41不同功能区为靶点,具有高活性和更好代谢性质的多肽及多肽类似物候选分子不断被发现,成为抗HIV药物研究领域的热点之一.本文综述了多肽和类肽类融合抑制剂的研究进展,为相关的药物开发和基础研究提供参考.The fusion of HIV and target cell membranes is mediated by the transmembrane glycoprotein gp41. HIV-1 fusion inhibitors target gp41 to prevent the virus-cell membrane fusion, thus interrupt the initial steps of viral replication. The first peptide fusion inhibitor （T-20） was approved by the U.S. FDA in 2003. However, the application of T-20 was limited by drawbacks such as rapid proteolysis, highly clinical dosage, poor patient adhesive and ineffectiveness to drug resistant HIV-1 isolates. In recent years, considerable progresses have been made in the understanding of the mechanism of fusion inhibitors and in the design of novel fusion inhibitors, to overcome the drawbacks of T-20. Various peptides and peptidomimetics used as fusion inhibitors have been developed, and these novel fusion inhibitors target different part of HIV-1 gp41 and show higher activity and better pharmacokinetic properties. In this paper, the recent progresses in the design and development of novel peptides and peptidominetics used as HIV-1 fusion inhibitors are reviewed, providing a reference for related drug development and basic research.

关 键 词：HIV-1 GP41 融合抑制剂 多肽 

分 类 号：R96[医药卫生—药理学]