Potent and selective inactivation of proteinases with N-peptidyl-O-acylhydroxylamines

The reaction of seven N-peptidyl-O-acyl hydroxylamines with serine proteinases exhibiting different substrate specificity has been investigated. Depending on the structure of the peptidyl residue of the inhibitors, rapid and complete irreversible inactivation of the enzymes may be achieved. Enzyme-catalyzed turnover of inhibitor to products was detected during reaction of proline-specific endopeptidase with N-Boc-Ala-Pro-O-(4-nitrobenzoyl)hydroxylamine.