On the degradation of dermorphin and D-Arg 2-dermorphin analogs by a soluble rat brain extract

Abstract

Degradation of dermorphin, [D-Arg 2]dermorphin and [D-Arg 2, Gly 3, Phe 4]dermorphin in a soluble rat brain extract was examined. The former two heptapeptides were degraded in a similar fashion to produce corresponding N-terminal tetrapeptide as the main degradation product along with the parallel release of Tyr 5, Pro 6 and Ser 7-NH 2. Tyr-D-Arg-Phe-Gly showed a good enzymatic stability. When captopril, an angiotensin-converting enzyme inhibitor, was present in the incubation mixture, hydrolysis of the Gly 4-Tyr 5 bond was markedly suppressed and resulted in release of the corresponding N-terminal hexapeptide as the main degradation product. Combined use of captopril and amastatin, an aminopeptidase inhibitor, markedly suppressed the hydrolysis of these peptides. On the other hand, [D-Arg 2, Gly 3, Phe 4]dermorphin was hydrolyzed easier than the other two heptapeptides and considerable amounts of Tyr 1 and Phe 4 were released after 20 hr incubation while the N-terminal tetrapeptide, Tyr-D-Arg-Gly-Phe, showed a good enzymatic stability. On the basis of these results, possible degradation pathways of these heptapeptides were discussed.