Development of peptidyl alpha-keto-beta-aldehydes as new inhibitors of cathepsin L--comparisons of potency and selectivity profiles with cathepsin B

Bioorg Med Chem Lett. 2000 Aug 7;10(15):1771-3. doi: 10.1016/s0960-894x(00)00340-1.

Abstract

We have utilized previously known substrate and inhibitor specificity profiles for the lysosomal cysteine protease, cathepsin L, to design a new series of putative inhibitors of this enzyme, based on di- and tri-peptidyl alpha-keto-beta-aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO, with a Ki 0.6 nM, to be the most potent, synthetic reversible inhibitor of cathepsin L reported to date.

Publication types

  • Comparative Study

MeSH terms

  • Aldehydes / chemistry*
  • Cathepsin B / antagonists & inhibitors*
  • Cathepsin B / metabolism
  • Cathepsin L
  • Cathepsins / antagonists & inhibitors*
  • Cathepsins / metabolism
  • Cysteine Endopeptidases
  • Cysteine Proteinase Inhibitors / chemistry
  • Cysteine Proteinase Inhibitors / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Endopeptidases*
  • Humans
  • Peptides / chemistry*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • Substrate Specificity

Substances

  • Aldehydes
  • Cysteine Proteinase Inhibitors
  • Peptides
  • Recombinant Proteins
  • Cathepsins
  • Endopeptidases
  • Cysteine Endopeptidases
  • Cathepsin B
  • CTSL protein, human
  • Cathepsin L