Potent peptide alpha-ketohydroxamate inhibitors of recombinant human calpain I

Bioorg Med Chem Lett. 2001 Oct 8;11(19):2615-7. doi: 10.1016/s0960-894x(01)00526-1.

Abstract

A series of potent dipeptide and tripeptide alpha-ketohydroxamic esters was prepared as inhibitors of recombinant human calpain I. Compound 3c, a Cbz-Leu-Phe hydroxamate, displayed the greatest potency against calpain I (IC(50)=6nM), while two compounds, 3l and 3m, both possessing the Cbz-Leu-Leu-Phe sequence, were the most potent (IC(50)=0.2 microM) in a MOLT-4 cell assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calpain / antagonists & inhibitors*
  • Cell Membrane Permeability / drug effects
  • Glycoproteins / chemical synthesis
  • Glycoproteins / chemistry
  • Glycoproteins / pharmacology*
  • Humans
  • Ketones / chemical synthesis
  • Ketones / chemistry
  • Ketones / pharmacology*
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Recombinant Proteins / antagonists & inhibitors
  • Structure-Activity Relationship
  • Tumor Cells, Cultured / drug effects

Substances

  • Glycoproteins
  • Ketones
  • Oligopeptides
  • Recombinant Proteins
  • calpain inhibitors
  • Calpain