Aza-peptide epoxides: a new class of inhibitors selective for clan CD cysteine proteases

J Med Chem. 2002 Nov 7;45(23):4958-60. doi: 10.1021/jm025581c.

Abstract

Aza-peptide epoxides, a new class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. The inhibitors have second-order rate constants up to 10(5) M(-1) s(-1), with the most potent epoxides having the S,S stereochemistry. The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition with other proteases such as chymotrypsin, papain, or cathepsin B.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Caspase Inhibitors
  • Cathepsin B / antagonists & inhibitors
  • Crystallography, X-Ray
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / chemistry
  • Epoxy Compounds / chemical synthesis*
  • Epoxy Compounds / chemistry
  • Kinetics
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Papain / antagonists & inhibitors
  • Plant Proteins / antagonists & inhibitors
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Aza Compounds
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Epoxy Compounds
  • Oligopeptides
  • Plant Proteins
  • Cysteine Endopeptidases
  • Cathepsin B
  • Papain
  • asparaginylendopeptidase