Structure-based design,synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors

被引：83

作者：

Ghosh, Arun K. ^{[1
]}

Xi, Kai

Grum-Tokars, Valerie

Xu, Xiaoming

Ratia, Kiira

Fu, Wentao

Houser, Katherine V.

Baker, Susan C.

Johnson, Michael E.

Mesecar, Andrew D.

机构：

[1] Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA

[2] Univ Illinois, Ctr Pharmaceut Biotechnol, Dept Med Chem & Pharmacognosy, Chicago, IL 60607 USA

[3] Loyola Univ Chicago, Stritch Sch Med, Dept Microbiol & Immunol, Maywood, IL USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 21期

关键词：

design; synthesis; SARS; 3CLpro; inhibitor; X-ray; structure;

D O I：

10.1016/j.bmcl.2007.08.031

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor I bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P-4-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5876 / 5880

页数：5

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