Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, in vitro

FEBS Lett. 1991 Mar 25;280(2):307-10. doi: 10.1016/0014-5793(91)80318-w.

Abstract

A series of new epoxysuccinyl peptides were designed and synthesized to develop a specific inhibitor of cathepsin B. Of these compounds, N-(L-3-trans-ethoxycarbonyloxirane-2-carbonyl)-L-isoleucyl-L-proli ne (compound CA-030) and N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-prol ine (compound CA-074) were the most potent and specific inhibitors of cathepsin B in vitro. The carboxyl group of proline and the ethyl ester group or the n-propylamide group in the oxirane ring were necessary, the ethyl ester group or the n-propylamide group being particularly effective for distinguishing cathepsin B from other cysteine proteinases such as cathepsins L and H, and calpains.

MeSH terms

  • Animals
  • Calpain / chemistry
  • Cathepsin B / antagonists & inhibitors*
  • Cathepsin H
  • Cathepsin L
  • Cathepsins / chemistry
  • Cysteine Endopeptidases*
  • Dipeptides / pharmacology*
  • Endopeptidases*
  • In Vitro Techniques
  • Leucine / analogs & derivatives
  • Leucine / pharmacology
  • Liver / drug effects
  • Liver / enzymology*
  • Rats

Substances

  • Dipeptides
  • N-(3-ethoxycarbonyloxirane-2-carbonyl)-isoleucyl-proline
  • N-(3-propylcarbamoyloxirane-2-carbonyl)-isoleucyl-proline
  • Cathepsins
  • Endopeptidases
  • Calpain
  • Cysteine Endopeptidases
  • Cathepsin B
  • Cathepsin L
  • Ctsl protein, rat
  • Cathepsin H
  • Ctsh protein, rat
  • Leucine
  • E 64