Inhibition of a membrane-bound enkephalin-degrading aminopeptidase by bestatin analogs

A variety of bestatin analogs were examined as potent inhibitors of a membrane-bound enkephalin-degrading aminopeptidase that was purified from monkey brain. Bestatinyl amino acid derivatives showed strong inhibition of this enzyme. The most effective was bestatin-L-Arg X AcOH, with a Ki value of 0.21 X 10(-8) M with Leu-enkephalin as substrate. It exhibited competitive kinetics and was about 100-fold more potent than bestatin. This compound seems to be useful for pharmacological and other studies.