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
收藏
页码：575 / 581
页数：7
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