Structure-based design of a macrocyclic inhibitor for peptide deformylase

被引：52

作者：

Hu, XB

Nguyen, KT

Verlinde, CLMJ

Hol, WGJ

Pei, DH

机构：

[1] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA

[2] Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA

[3] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[4] Univ Washington, Biomol Struct Ctr, Seattle, WA 98195 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 18期

关键词：

D O I：

10.1021/jm034113f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A macrocyclic, peptidomimetic inhibitor of peptide deformylase was designed by covalently cross-linking the P1' and PT side chains. The macrocycle, which contains an N-formylhydroxylamine side chain as the metal-chelating group, was synthesized from a diene precursor via olefin metathesis using Grubbs's catalyst. The cyclic inhibitor showed potent inhibitory activity toward Escherichia coli deformylase (K-I = 0.67 nM) and antibacterial activity against both Grampositive and Gram-negative bacteria (MIC = 0.7-12 mug/mL).

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页码：3771 / 3774

页数：4

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