Design, synthesis, and evaluation of inhibitors of Norwalk virus 3C protease

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5315-9. doi: 10.1016/j.bmcl.2011.07.016. Epub 2011 Jul 14.

Abstract

The first series of peptidyl aldehyde inhibitors that incorporate in their structure a glutamine surrogate has been designed and synthesized based on the known substrate specificity of Norwalk virus 3C protease. The inhibitory activity of the compounds with the protease and with a norovirus cell-based replicon system was investigated. Members of this class of compounds exhibited noteworthy activity both in vitro and in a cell-based replicon system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Chemistry Techniques, Synthetic
  • Crystallography, X-Ray
  • Cysteine Proteases / metabolism*
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Models, Molecular
  • Molecular Conformation
  • Norwalk virus / enzymology*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Cysteine Proteinase Inhibitors
  • Cysteine Proteases