Building the Pharmacophore Model of HIV-1 Integrase Strand Transfer Inhibitors and Studying Their Inhibition Mechanism

被引：3

作者：

吴可柱 ^{[1
,2
]}

李爱秀 ^{[1
,3
]}

刘兴太 ^{[1
]}

蔡德海 ^{[1
]}

马翼 ^{[4
]}

机构：

[1] Drug Design Laboratory of the Basic Science Department,Medical College of Chinese People′s Armed Police Force

[2] Department of Pharmacy,Jiangxi Provincial Corps Hospital of Chinese People's Armed Police Force

[3] Tianjin Key Laboratory for Biomarkers of Occupational and Environmental Hazard,Medical College of Chinese People′s Armed Police Force

[4] State Key Laboratory of Elemento-organic Chemistry,Nankai University

来源：

结构化学 | 2010年 / 29卷 / 04期

基金：

中国国家自然科学基金;

关键词：

HIV-1; integrase; strand transfer inhibitors; pharmacophore model; molecular docking; mechanism;

D O I：

10.14102/j.cnki.0254-5861.2010.04.026

中图分类号：

R96 [药理学];

学科分类号：

100602 ; 100706 ;

摘要：

The replication of HIV-1 requires the integration of its cyclic DNA into host DNA by HIV-1 integrase (IN), which includes two important reactions, 3’-processing and strand transfer, both catalyzed by HIV-1 IN. Disrupting either of the reactions will fulfill the purpose of inhibiting the replication of HIV-1. In this paper, pharmacophore modeling and molecular docking are employed to investigate the inhibition mechanism of the HIV-1 IN strand transfer inhibitors (INSTIs). Based on the results, we suggest that the inhibition mechanism of INSTIs involves the inhibitor chelating the cofactors Mg2+ and its forming hydrogen bonds with some crucial residues adjacent to the DDE active center.

引用

页码：575 / 581

页数：7

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