Enkephalinase: Selective peptide inhibitors

A unique, CNS membrane bound enkephalinase is described with greatest activities being measured in the striatum of the mouse. This enzyme was resistant to inhibition by puromycin and bestatin which are potent aminopeptidase inhibitors and to the angiotensin converting enzyme inhibitors, captopril and the free acid of MK-421, which were also very weak inhibitors of aminopeptidase. However, the glycopeptide, phosphoramidon, and the hydroxamic acids, HO-NHCOCH(CH₂CH(CH₃)₂)-CO-Ala-Gly-NH₂ and HO-NHCOCH(CH₂C₆H₅)-CO-Ala-Gly-NH₂, were potent enkephalinase inhibitors with IC₅₀'s (nM) of 39, 3.1 and 8.4, respectively. These peptides remain to be tested $\text{in}$$\text{vivo}$.