Protection of Chymotrypsin from Inactivation by a Nitrogen Mustard Antitumor Drug by Prior Acylation of the Active Center

Summary

The inactivation of a-chymotrypsin by chlorambucil has been blocked by prior acylation of the active site of the enzyme with p-nitrophenyl trimethylacetate. Trimethylacetyl-chymotrypsin which has been deacylated with hydroxylamine at pH 7.0 after exposure to chlorambucil exhibits full enzymic activity in contrast to the loss in activity shown by chlorambucil-treated chymotrypsin. These data suggest that inactivation of the enzyme occurs by reaction of the antitumor drug at the active site of the enzyme rather than at a nonspecific or allosteric site.