| 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[subscript i] 18 μM), leucine chloromethyl ketone (k[subscript i] 0.67 μM), and leucine bromomethyl ketone (K[subscript i] 0.20 μM), and the corresponding succinimido derivative (K[subscript i] 170 μM), succinamic acid derivative (K[subscript i] 6.9 μM), and phthalimido derivative (K[subscript i] 140 μM). 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. One of the above inhibitors, the succinamic acid derivative of leucine bromomethyl ketone, was successfully used a ligand in affinity chromatography. The blocked form of this inhibitor was coupled to aminomethyl cellulose and then deblocked in aqueous trifluoroacetic to yield and insolubilized analog of an NH₂-terminal L-leucine residue. ... |
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