title: N-peptidyl-O-carbamoyl amino acid hydroxamates: irreversible inhibitors for the study of the S2' specificity of cysteine proteinases.
abstract: A series of new inhibitors for cysteine proteinases with the general structure Z-Phe-Gly-NHO-CO-Aa (Aa = amino acids) was synthesized and tested as inhibitors of papain-like enzymes (cathepsins S, L, B and papain). Like N-peptidyl-O-acyl hydroxamates the inhibitors inactivate cysteine proteinases by a sulfenamidation of the active site cysteine residue. The most effective inhibitors display second order-rate constants of inactivation in the range of 10(3)-10(4) M-1.s-1. Since the structure of the N-peptidyl-O-carbamoyl amino acid hydroxamates allows the variation of the leaving group this class of inhibitors was used as a new tool for evaluation of the S2' specificity of cysteine proteinases.
authors: Institute of Biochemistry, Medical Faculty, Martin-Luther-University, Halle (Saale), Germany.
authors: D
authors: D
authors: Brömme
authors: H
authors: H
authors: Kirschke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010206:Papain / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity
chemical_list: D015853:Cysteine Proteinase Inhibitors; D006877:Hydroxamic Acids; D010206:Papain