D. Bromme et H. Kirschke, N-PEPTIDYL-O-CARBAMOYL AMINO-ACID HYDROXAMATES - IRREVERSIBLE INHIBITORS FOR THE STUDY OF THE S2' SPECIFICITY OF CYSTEINE PROTEINASES, FEBS letters, 322(3), 1993, pp. 211-214
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.