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

ABSTRACT: 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 1 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.

SUBMITTER: Ghosh AK

PROVIDER: S-EPMC2112940 | biostudies-other | 2007 Nov

REPOSITORIES: biostudies-other

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

Ghosh Arun K AK Xi Kai K Grum-Tokars Valerie V Xu Xiaoming X Ratia Kiira K Fu Wentao W Houser Katherine V KV Baker Susan C SC Johnson Michael E ME Mesecar Andrew D AD

Bioorganic & medicinal chemistry letters 20070819 21

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 1 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 ...[more]

PMID: 17855091

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