Inhibition of human leukocyte elastase by acetyl and trifluoroacetyl oligopeptide chloromethyl ketones.

Abstract

The action of human leukocyte elastase on a series of acetyl and trifluoroacetyl tri-, tetra-, and pentapeptide chloromethyl ketones has been investigated. Leukocyte and pancreatic elastases react quite differently with these irreversible inhibitors. For instance, leukocyte elastase has a much lower affinity for the compounds than pancreatic elastase. On the other hand, the inhibition rate constants of the two enzymes are not influenced in the same way by peptide chain elongation. The two elastases, however, share a common property: trifluoroacetyl tri- and tetraalanine chloromethyl ketones are more tightly bound but are less reactive than the corresponding acetylated inhibitors. This behavior is probably due to the formation of nonproductive complexes between the enzymes and the trifluoroacetylated inhibitors.