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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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 P4-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.

Original languageEnglish (US)
Pages (from-to)5876-5880
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number21
DOIs
StatePublished - Nov 1 2007

Keywords

  • Design
  • Inhibitor
  • SARS 3CLpro
  • Synthesis
  • X-ray structure

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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