Inhibition of porcine elastase and anhydroelastase by boronic acids

Abstract

Porcine pancreatic elastase binds and is inhibited by the arylboronic acids with K i values on the order of 10 −4 m, binding tighter than butaneboronic acid or methaneboronic acid. The pH dependence of the K i values shows two p K values, p K 1 = 6.8, assigned to enzyme ionization, and p K 2, assigned to inhibitor ionization. The substituent effect of the arylboronic acids on K i , investigated by a Hammett plot, suggests that the boron atom of the inhibitor interacts strongly with a nucleophilic site of elastase and probably forms an enzyme-bound tetrahedral structure. Anhydroelastase was formed by the removal of active site Ser-OH of elastase. Anhydroelastase has a much reduced affinity for the arylboronic acids or specific aldehyde inhibitors than the native enzyme, agreeing with the tetrahedral postulate.