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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:17

Article

Ghosh, Arun K. ; Xi, Kai ; Grum-Tokars, Valerie ; Xu, Xiaoming ; Ratia, Kiira ; Fu, Wentao ; Houser, Katherine V. ; Baker, Susan C. ; Johnson, Michael E. ; Mesecar, Andrew D.

关键词: design;    synthesis;    SARS 3CLpro;    inhibitor;    X-ray;    structure;   

DOI  :  10.1016/j.bmcl.2007.08.031

来源: Elsevier

【 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.

【 授权许可】

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