Inhibition of [gamma]-endorphin generating endopeptidase activity of rat brain by peptides: Structure activity relationship

Abstract

Gamma-Endorphin generating endopeptidase (gammaEGE) activity is an enzyme activity which converts beta-endorphin into gamma-endorphin and beta-endorphin-(18–31). The inhibitory potency on gammaEGE activity of neuropeptides and analogues or fragments of neuropeptides was tested. Dynorphin-(1–13) (IC50: 0.14 μM), human beta-endorphin-(1–31) (IC50: 15.5 μM), porcine ACTH-(1–39) (IC50: 6.3 μM), and substance P (IC50: 26 μM) had an inhibitory activity on gammaEGE activity. beta-Endorphin-(18–31) (IC50: 0.35 μM) but not gamma-endorphin potently inhibited gammaEGE activity. The IC50 of poly (Lys)40–60 was 0.8 μM. It is concluded that 1) gammaEGE activity is strongly inhibited by its product beta-endorphin-(18–31), 2) the enzyme is strongly inhibited by peptides with an aromatic amino acid at the NH2-terminal and/or basic amino acids in the COOH-terminal of the peptide chain