Metalloform-selective inhibition: Synthesis and structure-activity analysis of Mn(II)-form-selective inhibitors of Escherichia coli methionine aminopeptidase

doi:10.1016/j.bmcl.2005.09.019

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	Metalloform-selective inhibition: Synthesis and structure-activity analysis of Mn(II)-form-selective inhibitors of Escherichia coli methionine aminopeptidase
	Huang, QQ ; Huang, M; Nan, FJ; Ye, QZ
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2005-12-15
卷号	15 期号:24 页码:5386-5391
关键词	methionine aminopeptidase metalloform-selective inhibitor synthesis
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2005.09.019
文献子类	Article
英文摘要	Methionine aminopeptidase (MetAP) is a promising target for development of novel antibacterial, antifungal and anticancer agents. However, its physiologically relevant metal ion remains to be defined, and its inhibitors need to inhibit the in vivo metalloform. Based on the Mn(II)-form-selective inhibitors discovered by high throughput screening as leads, a series of analogs of 5-phenylfuran-2-carboxylic acid was prepared and subsequently evaluated on Co(II)-, Mn(II)-, Ni(II)-, and Fe(II)-forms of Escherichia coli MetAP, in order to define the structural elements responsible for their inhibitory potency and metalloform selectivity. Various substitutions on the phenyl ring changed their potency on the Mn(II)-form but not their metalloform selectivity. We conclude that the preferential coordination of the carboxyl group to Mn(II) ions is the major determinant for their superb selectivity toward the Mn(H)-form. Changing the carboxylate to hydroxamate alters its ability to bind and discriminate different metal ions, and the hydroxamate derivative becomes non-selective among the metalloforms tested. (c) 2005 Elsevier Ltd. All rights reserved.
资助项目	NIAID NIH HHS[R01 AI065898] ; NCRR NIH HHS[P20 RR15563] ; NCRR NIH HHS[P20 RR16475]
WOS关键词	SPECIFICITY ; OVALICIN ; COFACTOR ; ENZYME ; TARGET ; GENE
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000233206300006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273754]
专题	国家新药筛选中心
通讯作者	Nan, FJ
作者单位	1.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Chinese Natl Ctr Drug Screening,Shanghai Inst Mat, Shanghai 201203, Peoples R China 2.Univ Kansas, High Troughput Screening Lab, Lawrence, KS 66047 USA
推荐引用方式 GB/T 7714	Huang, QQ,Huang, M,Nan, FJ,et al. Metalloform-selective inhibition: Synthesis and structure-activity analysis of Mn(II)-form-selective inhibitors of Escherichia coli methionine aminopeptidase[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2005,15(24):5386-5391.
APA	Huang, QQ,Huang, M,Nan, FJ,&Ye, QZ.(2005).Metalloform-selective inhibition: Synthesis and structure-activity analysis of Mn(II)-form-selective inhibitors of Escherichia coli methionine aminopeptidase.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,15(24),5386-5391.
MLA	Huang, QQ,et al."Metalloform-selective inhibition: Synthesis and structure-activity analysis of Mn(II)-form-selective inhibitors of Escherichia coli methionine aminopeptidase".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 15.24(2005):5386-5391.