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 stoichiometric inhibition of papain at less than 100 μM concentration under conditions where formation of the corresponding aldehyde is negligible. Oxidation of the active site thiolate by the bound peroxide is believed to lead to formation of an inactive sulfenate or sulfenic acid. Reduction of the ozonide in excess DMSO provides a convenient method for in situ generation of a peptide aldehyde.