N-PEPTIDYL-O-CARBAMOYL AMINO-ACID HYDROXAMATES - IRREVERSIBLE INHIBITORS FOR THE STUDY OF THE S2' SPECIFICITY OF CYSTEINE PROTEINASES

A series of new inhibitors for cysteine proteinases with the general s tructure Z-Phe-Gly-NHO-CO-Aa (Aa = amino acids) was synthesized and te sted as inhibitors of papain-like enzymes (cathepsins S, L, B and papa in). Like N-peptidyl-0-acyl hydroxamates the inhibitors inactivate cys teine proteinases by a sulfenamidation of the active site cysteine res idue. The most effective inhibitors display second order-rate constant s of inactivation in the range of 10(3)-10(4) M-1.s-1. Since the struc ture of the N-peptidyl-0-carbamoyl amino acid hydroxamates allows the variation of the leaving group this class of inhibitors was used as a new tool for the evaluation of the S2' specificity of cysteine protein ases.