Peroxides as oxidative enzyme inhibitors: Mechanism-based inhibition of a cysteine protease by an amino acid ozonide

A stable ozonide derived from Cbz-L-Phe accomplishes rapid and stoichiometr ic inhibition of papain at less than 100 mu M concentration under condition s where formation of the corresponding aldehyde is negligible. Oxidation of the active site thiolate by the bound peroxide is believed to lead to form ation of an inactive sulfenate or sulfenic acid. Reduction of the ozonide i n excess DMSO provides a convenient method for in situ generation of a pept ide aldehyde. (C) 1999 Elsevier Science Ltd. All rights reserved.