Peptidyl aldehyde inhibitors of calpain incorporating P2-proline mimetics

Bioorg Med Chem Lett. 2003 Mar 10;13(5):783-4. doi: 10.1016/s0960-894x(03)00021-0.

Abstract

Four new peptidyl aldehydes bearing proline mimetics at the P(2)-position were synthesized and studied as inhibitors of calpain I, cathepsin B, and selected serine proteases. The ring size of the P(2)-constraining residue influenced the inhibitory potency and selectivity of the compounds for calpain I compared to the other proteases.

Publication types

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

MeSH terms

  • Aldehydes / chemical synthesis
  • Aldehydes / pharmacology*
  • Animals
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / pharmacology*
  • Calpain / antagonists & inhibitors*
  • Cathepsin B / antagonists & inhibitors
  • Cysteine Proteinase Inhibitors / chemical synthesis
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Humans
  • Liver / enzymology
  • Oligopeptides / chemical synthesis
  • Oligopeptides / pharmacology*
  • Proline / chemistry*
  • Serine Proteinase Inhibitors / chemical synthesis
  • Serine Proteinase Inhibitors / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Swine

Substances

  • Aldehydes
  • Cysteine Proteinase Inhibitors
  • Oligopeptides
  • Serine Proteinase Inhibitors
  • Proline
  • Calpain
  • Cathepsin B