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

	D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75
	Du L 1; Chen JX 2; Chen J 1; Yang LM 3; Zheng YT 3; Tang Y2; Shen X1,2; Jiang HL 1,2; ytang234@ecust.edu.cn ; xshen@mail.shcnc.ac.cn
	2008
发表期刊	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN	0006-291X
卷号	375 期号:1 页码:139-144
合作性质	其它
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.
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
资助者	This work was finan- cially supported by the National Natural Science Foundation of China (Grants Nos. 30525024, 20472095, 20572023), the National ‘‘863” project of China 2006AA609Z447 and 2006AA609Z41), Shanghai Pujiang Program No. 05PJ14034), Shanghai Key Basic Research Project (Grants Nos. 06JC14080, 05JC14092), the State Key Program of Basic Research of China (Grants Nos. 2004CB58905, 2006AA09Z447), and the grant from CAS (Grant No. KSCX2-YW-R-18). ; This work was finan- cially supported by the National Natural Science Foundation of China (Grants Nos. 30525024, 20472095, 20572023), the National ‘‘863” project of China 2006AA609Z447 and 2006AA609Z41), Shanghai Pujiang Program No. 05PJ14034), Shanghai Key Basic Research Project (Grants Nos. 06JC14080, 05JC14092), the State Key Program of Basic Research of China (Grants Nos. 2004CB58905, 2006AA09Z447), and the grant from CAS (Grant No. KSCX2-YW-R-18). ; This work was finan- cially supported by the National Natural Science Foundation of China (Grants Nos. 30525024, 20472095, 20572023), the National ‘‘863” project of China 2006AA609Z447 and 2006AA609Z41), Shanghai Pujiang Program No. 05PJ14034), Shanghai Key Basic Research Project (Grants Nos. 06JC14080, 05JC14092), the State Key Program of Basic Research of China (Grants Nos. 2004CB58905, 2006AA09Z447), and the grant from CAS (Grant No. KSCX2-YW-R-18). ; This work was finan- cially supported by the National Natural Science Foundation of China (Grants Nos. 30525024, 20472095, 20572023), the National ‘‘863” project of China 2006AA609Z447 and 2006AA609Z41), Shanghai Pujiang Program No. 05PJ14034), Shanghai Key Basic Research Project (Grants Nos. 06JC14080, 05JC14092), the State Key Program of Basic Research of China (Grants Nos. 2004CB58905, 2006AA09Z447), and the grant from CAS (Grant No. KSCX2-YW-R-18).
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收录类别	其他
语种	英语
资助者	This work was finan- cially supported by the National Natural Science Foundation of China (Grants Nos. 30525024, 20472095, 20572023), the National ‘‘863” project of China 2006AA609Z447 and 2006AA609Z41), Shanghai Pujiang Program No. 05PJ14034), Shanghai Key Basic Research Project (Grants Nos. 06JC14080, 05JC14092), the State Key Program of Basic Research of China (Grants Nos. 2004CB58905, 2006AA09Z447), and the grant from CAS (Grant No. KSCX2-YW-R-18). ; This work was finan- cially supported by the National Natural Science Foundation of China (Grants Nos. 30525024, 20472095, 20572023), the National ‘‘863” project of China 2006AA609Z447 and 2006AA609Z41), Shanghai Pujiang Program No. 05PJ14034), Shanghai Key Basic Research Project (Grants Nos. 06JC14080, 05JC14092), the State Key Program of Basic Research of China (Grants Nos. 2004CB58905, 2006AA09Z447), and the grant from CAS (Grant No. KSCX2-YW-R-18). ; This work was finan- cially supported by the National Natural Science Foundation of China (Grants Nos. 30525024, 20472095, 20572023), the National ‘‘863” project of China 2006AA609Z447 and 2006AA609Z41), Shanghai Pujiang Program No. 05PJ14034), Shanghai Key Basic Research Project (Grants Nos. 06JC14080, 05JC14092), the State Key Program of Basic Research of China (Grants Nos. 2004CB58905, 2006AA09Z447), and the grant from CAS (Grant No. KSCX2-YW-R-18). ; This work was finan- cially supported by the National Natural Science Foundation of China (Grants Nos. 30525024, 20472095, 20572023), the National ‘‘863” project of China 2006AA609Z447 and 2006AA609Z41), Shanghai Pujiang Program No. 05PJ14034), Shanghai Key Basic Research Project (Grants Nos. 06JC14080, 05JC14092), the State Key Program of Basic Research of China (Grants Nos. 2004CB58905, 2006AA09Z447), and the grant from CAS (Grant No. KSCX2-YW-R-18).
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/4627
专题	科研部门_分子免疫药理学（郑永唐）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	ytang234@ecust.edu.cn; xshen@mail.shcnc.ac.cn
作者单位	1.Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China 2.School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China 3.Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
推荐引用方式 GB/T 7714	Du L,Chen JX,Chen J,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 L.,Chen JX.,Chen J.,Yang LM.,Zheng YT.,...&xshen@mail.shcnc.ac.cn.(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 L,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.

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