Altstein, M., Department of Neurobiology, The Weizmann Institute of Science, P.O.B. 26, Rehovot, 76100, Israel
Bachar, E., Department of Neurobiology, The Weizmann Institute of Science, P.O.B. 26, Rehovot, 76100, Israel
Vogel, Z., Department of Neurobiology, The Weizmann Institute of Science, P.O.B. 26, Rehovot, 76100, Israel
Blumberg, S., Department of Biophysics, The Weizmann Institute of Science, P.O.B. 26, Rehovot, 76100, Israel

Metal ion-chelating agents inhibited enkephalin degradation by a rat striatal membrane-associated endopeptidase termed 'enkephalinase'. The combination of a hydrophobic dipeptidyl moiety and a transition metal-chelating moiety in the same molecule resulted in very efficient and selective inhibitors of enkephalinase. The mercaptoacetyl dipeptides (2-mercaptoacetyl-Leu-Phe and 2-mercaptoacetyl-Phe-Leu) and the N-phosphorylated dipeptides (phosphoryl-Leu-Phe and phosphoramidon) inhibited enkephalinase with IC50 values of 15, 70, 0.3 and 1 nM respectively, but were much less potent against the aminopeptidase and angiotensin converting enzyme, two other metalloenzymes implicated in the degradation of the enkephalins in brain. The inhibition of enkephalinase, using phosphoryl-Leu-Phe as a selective inhibitor, resulted in a 4 fold increase in the amount of enkephalin recovered following K+ depolarization of rat striatal slices. © 1983.