Peptidyl aldehyde inhibitors of calpain incorporating P2-proline mimetics

Four new peptidyl aldehydes bearing proline mimetics at the P2-position were synthesized and studied as inhibitors of calpain I, cathepsin B, and selected serine proteases. The ring size of the P2-constraining residue influenced the inhibitory potency and selectivity of the compounds for calpain I compared to the other proteases.