Kinetics of inhibition of Aeromonas aminopeptidase by leucine methyl ketone derivatives

Abstract

A number of methyl ketones have been prepared from l-leucine and found to be competitive inhibitors of Aeromonas aminopeptidase. These inhibitors were leucine methyl ketone (K i 18 μ m), leucine chloromethyl ketone (K i 0.67 μ m), and leucine bromomethyl ketone (K i 0.20 μ m), and the corresponding succinimido derivative (K i 170 μ m), succinamic acid derivative (K i 6.9 μ m) and phthalimido derivative (K i 140 μ m). Reversible inhibition was observed for all of the inhibitors tested, indicating that the active site of this enzyme is not alkylated or acylated by the nucleophile-sensitive components of some of the inhibitors. The chloromethyl ketones derived from l-leucine and l-phenylalanine were found to have the same relative binding constants as the substrates, l-leucinamide and l-phenylalaninamide.