Stability of His-Phe-Arg-Trp-Pro-Gly-Pro to Leucine Aminopeptidase, Carboxypeptidase Y, and Rat Nasal Mucus, Blood, and Plasma

Abstract

The His-Phe-Arg-Trp-Pro-Gly-Pro [ACTH-(6–9)-PGP] peptide was synthesized. Proteolysis of ACTH-(6–9)-PGP and semax (Met-Glu-His-Phe-Pro-Gly-Pro) in the presence of leucine aminopeptidase and carboxypeptidase Y was studied. If the proteolysis of ACTH-(6–9)-PGP is mainly defined by aminopeptidases, the basic metabolite is Trp-Pro-Gly-Pro. Identification of major metabolites of ACTH-(6–9)PGP when incubated with the enzymes in vitro made it possible to evaluate proteolysis pathways of the peptide and prepare necessary amounts of its metabolites for using them as standards. Kinetics of ACTH-(6–9)PGP degradation in the presence of enzyme systems of nasal mucus, blood, and plasma were also explored. It was found that proteolysis of ACTH-(6–9)-PGP in rat blood and plasma occurs mainly under the effect of enzymes whose action is similar to leucine aminopeptidase.