SUBSITE REQUIREMENTS FOR PEPTIDE ALDEHYDE INHIBITORS OF HUMAN CALPAIN-I

Dipeptide and tripeptide aldehydes have been evaluated as inhibitors o f human calpain I. Dipeptide aldehydes are generally equipotent with t ripeptide aldehydes. Calpain I possesses a rather stringent requiremen t for Leu at P-2, but accepts a variety of capping groups and amino ac ids at P-1 and P-3. Several new peptide aldehydes that are more potent than previously reported calpain I inhibitors have been identified. ( C) 1997 Elsevier Science Ltd.