Inhibitory effect of di- and tripeptidyl aldehydes on calpains and cathepsins

J Enzyme Inhib. 1990;3(3):195-201. doi: 10.3109/14756369009035837.


Eight different di- and tripeptidyl aldehyde derivatives, each having at its C-terminus an aldehyde analog of L-norleucine, L-methionine, or L-phenylalanine with a preceding L-leucine residue, were synthesized and tested for their inhibitory effects on several serine and cysteine endopeptidases. These compounds showed almost no inhibition of trypsin, and only weak inhibition of alpha-chymotrypsin and cathepsin H, while they exhibited marked inhibition of cathepsin B less than calpain II congruent to calpain I less than cathepsin L, being stronger in this order. The mode of inhibition of these cysteine proteinases was competitive for the peptide substrate used and inhibitor constants (Ki) were calculated from the Dixon plot. The best inhibitors found were: 4-phenyl-butyryl-Leu-Met-H for calpain I (Ki, 36 nM) and calpain II (Ki, 50 nM); acetyl-Leu-Leu-nLeu-H for cathepsin L (Ki, 0.5 nM); acetyl-Leu-Leu-Met-H for cathepsin B (Ki, 100 nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemical synthesis
  • Aldehydes / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Calpain / antagonists & inhibitors*
  • Cathepsins / antagonists & inhibitors*
  • Dipeptides / chemical synthesis
  • Dipeptides / pharmacology*
  • Erythrocytes / enzymology
  • Humans
  • Indicators and Reagents
  • Kidney / enzymology
  • Kinetics
  • Molecular Sequence Data
  • Oligopeptides / chemical synthesis
  • Oligopeptides / pharmacology*
  • Protease Inhibitors / chemical synthesis*
  • Rats
  • Structure-Activity Relationship
  • Swine


  • Aldehydes
  • Dipeptides
  • Indicators and Reagents
  • Oligopeptides
  • Protease Inhibitors
  • Cathepsins
  • Calpain