Structure-based identification of small molecule compounds targeting cell cyclophilin A with anti-HIV-1 activity

doi:10.1016/j.ejphar.2007.03.023

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	Structure-based identification of small molecule compounds targeting cell cyclophilin A with anti-HIV-1 activity
	Chen, Shuai ; Zhao, Xuemei ; Tan, Jinzhi ; Lu, Hong ; Qi, Zhi ; Huang, Qiang ; Zeng, Xianzhuo ; Zhang, Mingjun ; Jiang, Shibo ; Jiang, Hualiang
刊名	EUROPEAN JOURNAL OF PHARMACOLOGY
	2007-06-22
卷号	565 期号:1-3 页码:54-59
关键词	cyclophilin A cyclosporin A human immunodeficiency virus peptidyl-prolyl cis-trans isomerase
ISSN号	0014-2999
DOI	10.1016/j.ejphar.2007.03.023
文献子类	Article
英文摘要	Cyclophilin A acts as protein folding chaperones and intracellular transports in many cellular processes. Previous studies have shown that cyclophilin A can interact with HIV-1 (human immunodeficiency virus type 1) gag protein and enhance viral infectivity. Many cyclophilin A inhibitors such as cyclosporin A can inhibit HIV-1 replication in vitro. Here, we report a structure-based identification of novel non-peptidic cyclophilin A inhibitors as anti-HIV lead compounds. Following a computer-aided virtual screening and subsequent surface plasmon resonance (SPR) analysis, 12 low molecular weight cyclophilin A ligands were selected for further evaluation of their in vitro inhibition of peptidyl-prolyl cis-trans isomerase (PPlase) activity of cyclophilin A and HIV-1 replication. Five of these compounds (FD5, FD8, FD9, FD10 and FD12) exhibited inhibition against both PPlase activity and HIV-1 infection. These active compounds will be used as leads for structure and activity relationship (SAR) and optimization studies in order to design more effective anti-HIV-1 therapeutics, and as probes for investigating the effect of cyclophilins on HIV-1 replication. (c) 2007 Elsevier B.V. All rights reserved.
资助项目	NIAID NIH HHS[R01 AI046221] ; NIAID NIH HHS[AI46221] ; NIAID NIH HHS[R01 AI046221-04] ; NIAID NIH HHS[R21 AI046221]
WOS关键词	IMMUNODEFICIENCY-VIRUS TYPE-1 ; HIGHLY INHIBITORY-ACTIVITY ; CYCLOSPORINE-A ; BIOLOGICAL EVALUATION ; BINDING-PROTEIN ; HIV-1 VIRIONS ; SITE ; INFECTIVITY ; CALCINEURIN ; ISOMERASE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000247336500007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273222]
专题	药物发现与设计中心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	Jiang, Hualiang
作者单位	1.Fudan Univ, Sch Life Sci, Inst Genet, State Key Lab Genet Engn, Shanghai, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Beijing 100864, Peoples R China 3.New York Blood Ctr, Lindsley F Kimball Res Inst, Lab Viral Immunol, New York, NY 10021 USA
推荐引用方式 GB/T 7714	Chen, Shuai,Zhao, Xuemei,Tan, Jinzhi,et al. Structure-based identification of small molecule compounds targeting cell cyclophilin A with anti-HIV-1 activity[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2007,565(1-3):54-59.
APA	Chen, Shuai.,Zhao, Xuemei.,Tan, Jinzhi.,Lu, Hong.,Qi, Zhi.,...&Yu, Long.(2007).Structure-based identification of small molecule compounds targeting cell cyclophilin A with anti-HIV-1 activity.EUROPEAN JOURNAL OF PHARMACOLOGY,565(1-3),54-59.
MLA	Chen, Shuai,et al."Structure-based identification of small molecule compounds targeting cell cyclophilin A with anti-HIV-1 activity".EUROPEAN JOURNAL OF PHARMACOLOGY 565.1-3(2007):54-59.