D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75

doi:10.1016/j.bbrc.2008.07.139

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75
	Du, Li 1; Chen, Jing2 ; Yang, Liumeng 1,3; Zheng, Yongtang 3; Tang, Yun 2; Shen, Xu1,2 ; Jiang, Hualiang1,2
刊名	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
	2008-10-10
卷号	375 期号:1 页码:139-144
关键词	HIV-1 integrase Lens epithelium-derived growth factor (LEDGF/p75) yeast two-hybrid assay surface plasmon resonance (SPR) molecular docking site-directed mutagenesis
ISSN号	0006-291X
DOI	10.1016/j.bbrc.2008.07.139
文献子类	Article
英文摘要	Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. Since LEDGF/p75 plays an important role in HIV integration, disruption of the LEDGF/p75 interaction with IN has provided a special interest for anti-HIV agent discovery. in this work, we reported that a benzoic acid derivative, 4-[(5-bromo-4-{[2,4-dioxo-3-(2-oxo-2-phenylethyl)-1,3-thiazolidin-5-ylidene]methyl)-2-ethoxyphenoxy)methyl] benzoic acid (D77) could potently inhibit the IN-LEDGF/p75 interaction and affect the HIV-1 IN nuclear distribution thus exhibiting antiretroviral activity. Molecular docking with site-directed mutagenesis analysis and Surface plasmon resonance (SPR) binding assays has clarified possible binding mode of D77 against HIV-1 integrase. As the firstly discovered small molecular compound targeting HIV-1 integrase interaction with LEDGF/p75, D77 might Supply useful structural information for further anti-HIV agent discovery. (C) 2008 Elsevier Inc. All rights reserved.
资助项目	National Natural Science Foundation of China[30525024] ; National Natural Science Foundation of China[20472095] ; National Natural Science Foundation of China[20572023] ; National "863" project of China[2006AA609Z447] ; National "863" project of China[2006AA609Z41] ; Shanghai Pujiang Program[05PJ14034] ; Shanghai Key Basic Research Projec[06JC14080] ; Shanghai Key Basic Research Projec[05JC14092] ; State Key Program of Basic Research of China[2004CB58905] ; State Key Program of Basic Research of China[2006AA09Z447] ; CAS[KSCX2-YW-R-18]
WOS关键词	HIV-1 INTEGRASE ; CATALYTIC DOMAIN ; COACTIVATOR P75 ; GROWTH-FACTOR ; FORCE-FIELD ; HUMAN-CELLS ; PROTEIN ; DNA ; IDENTIFICATION ; VALIDATION
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000259253800027
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272782]
专题	药理学第三研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Shen, Xu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 2.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China; 3.Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Lab Mol Immunopharmacol, Kunming 650223, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Du, Li,Chen, Jing,Yang, Liumeng,et al. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2008,375(1):139-144.
APA	Du, Li.,Chen, Jing.,Yang, Liumeng.,Zheng, Yongtang.,Tang, Yun.,...&Jiang, Hualiang.(2008).D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,375(1),139-144.
MLA	Du, Li,et al."D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 375.1(2008):139-144.