以HIV-1 IN-LEDGF/p75相互作用为靶点的抑制剂筛选  

Screening of inhibitors targeting HIV-1 IN-LEDGF/p75 interaction

作　　者：许晓双 张大为 XU Xiao-shuang;ZHANG Da-wei(Institute of Bioinformatics and Medical Engineering,Jiangsu University of Technology,Changzhou 213001,China)

机构地区：[1]江苏理工学院生物信息与医药工程研究所,常州213001

出　　处：《中国医药生物技术》2018年第6期493-499,共7页Chinese Medicinal Biotechnology

基　　金：国家自然科学基金(31700297)

摘　　要：目的晶状体上皮源性生长因子p^(75)蛋白(LEDGF/p75)与HIV-1整合酶(IN)之间的蛋白-蛋白相互作用是开发抗HIV-1药物的有效靶点,本文旨在寻找以HIV-1IN-LEDGF/p75相互作用为靶点的小分子抑制剂。方法采用均相时间分辨荧光技术(HTRF)筛选了799个化合物,比对IN-LEDGF/p75相互作用的抑制活性。结果发现5个化合物——肾上腺酮、6-溴-1,2-二氢萘-1,2-二酮、头孢噻吩、根皮含柘树呫吨酮L和迷迭香酸对该相互作用表现出不同程度的抑制作用,其IC50值分别为12.3、22.7、26.2、18.5和1.13μmol/L。结论为HIV-1IN-LEDGF/p75相互作用抑制剂的发现以及新的抗HIV-1药物的开发提供了重要基础。Objective The protein-protein interaction between the cellular chromatin associated protein lens epithelium-derived growth factor （LEDGF/p75） and the HIV-1 integrase （IN） is an effective target for the development of anti-HIV-1 drugs. This work aims to find small molecular inhibitors targeting the HIV-1 IN-LEDGF/p75 interaction. Methods The inhibitory activity of 799 compounds （from 2 compounds libraries： InterBioScreen and BioBioPha） on the interaction of IN-LEDGF/p75 was screened by a homogeneous time resolved fluorescence （HTRF）-based assay.Results It was found that five compounds, adrenalone, bonaphton, cefalotin, cudraxanthone L and rosmarinic acid, showed different inhibitory effect on the interaction of HIV-1 IN-LEDGF/p75, and their IC50 values were 12.3, 22.7, 26.2, 18.5 and 1.13 μmol/L, respectively. Conclusion This work provides an important basis for the discovery of HIV-1 IN-LEDGF/p75 interaction inhibitors and the development of new anti-HIV-1 drugs.

关 键 词：HIV整合酶 HIV整合酶抑制剂 LEDGF/p75 均相时间分辨荧光技术 蛋白-蛋白相互作用 

分 类 号：R94[医药卫生—药剂学]