Subsite requirements for peptide aldehyde inhibitors of human calpain I

Abstract

Dipeptide and tripeptide aldehydes have been evaluated as inhibitors of human calpain I. Dipeptide aldehydes are generally equipotent with tripeptide aldehydes. Calpain I possesses a rather stringent requirement for Leu at P 2, but accepts a variety of capping groups and amino acids at P 1 and P 3. Several new peptide aldehydes that are more potent than previously reported calpain I inhibitors have been identified.