The selective inactivation of thiol proteasesin vitro andin vivo

Peptidyl diazomethyl ketone derivatives inactivate thiol proteases by affinity labeling. The peptide sequence permits the reagents to be targeted to individual proteases according to their specificity. Alkylation of the active center thiol group takes place. The reagents are not reactive to simple thiols such as mercaptoethanol and appear to inactivate thiol proteases by acting as suicide substrates. Other classes of proteases are not affected. Initial results indicate that peptidyl diazomethyl ketones can also be used to inactivate thiol proteases in vivo.