Ⅰ型人类免疫缺陷病毒整合酶及其抑制剂研究进展  

Research progress on HIV-1 integrase and its inhibitors

作　　者：吴可柱[1] 李爱秀[1,2] 

机构地区：[1]中国人民武装警察部队医学院基础部,天津300162 [2]中国人民武装警察部队医学院职业与环境危害生物标志物天津市重点实验室,天津300162

出　　处：《沈阳药科大学学报》2009年第2期157-164,共8页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(30472166);天津市科技攻关计划重点科技攻关专项基金资助项目(06YFGZSH07000);武警部队科研基金资助项目(WKH2003003)

摘　　要：目的为研究新型Ⅰ型人类免疫缺陷病毒(human immunodeficiency virus type-1,HIV-1)整合酶抑制剂提供参考。方法根据查阅的文献从HIV-1整合酶的结构与功能、HIV-1整合酶的催化机制、HIV-1整合酶抑制剂对整合酶作用环节的影响等方面进行综述。结果HIV-1整合酶是由288个氨基酸残基组成的蛋白质,由病毒pol基因编码,相对分子质量约为32000;HIV-1整合酶抑制剂通过干扰整合酶的多聚化、竞争性结合病毒DNA长末端重复序列、阻断整合酶的"3′-加工"(切割病毒DNA)和"链转移"等影响整合酶的作用。结论利用先进的计算机辅助药物设计手段,通过对现有抑制剂构效关系以及抑制剂与大分子作用方式的研究可以逐步阐明整合酶抑制剂的作用机制;应着眼于寻找高活性的整合酶抑制剂,为治疗艾滋病提供新的途径。Objective To provide reference for our studies in designing new inhibitors of human immunodeficiency virus type-1 （HIV-1 ）integrase. Methods According to the literature gathered,this article reviewed the structure, the function, and the catalytic mechanism of HIV- 1 integrase, besides, the effect of inhibitors to the HIV- 1 integrase in the different steps of the whole process was also reviewed. Results The HIV- 1 integrase ,a kind of protein,coded by the pol gene was composed of 288 amino acid resides and its relative molecular mass was 32 000. The inhibitors effectively influenced the HIV- 1 integrase by interfering with the oligomerization of HIV- 1 integrase, competitively binding with the DNA long terminal repeat, and intercepting the 3＇-processing and strand transfer in the whole process. Conclusions Utilizing advanced means of computer aided drug design, it is possible to gradually elucidate the mechanism of action of the inhibitors by studying the structure-activity relationship of the existing inhibitors and the action mode between the inhibitors and the macromolecule. Thus, emphasis should be laid to search for new integrase inhibitors with high activities to provide a new way of treating AIDS.

关 键 词：I型人类免疫缺陷病毒 整合酶 抑制剂 

分 类 号：R97[医药卫生—药品]