Potent peptide α-Ketohydroxamate inhibitors of recombinant human calpain I

A series of potent dipeptide and tripeptide α-ketohydroxamic esters was prepared as inhibitors of recombinant human calpain I. Compound 3c, a Cbz-Leu-Phe hydroxamate, displayed the greatest potency against calpain I (IC50=6 nM), while two compounds, 3l and 3m, both possessing the Cbz-Leu-Leu-Phe sequence, were the most potent (IC50=0.2 μM) in a MOLT-4 cell assay.