Stability In Vitro of 5-oxo-Pro-Arg-Pro, 5-oxo-Pro-His-Pro-Gly-ProNH2, and Phe-Pro-Leu-Pro-Ala

Abstract

Proteolysis of 5-oxo-Pro-Arg-Pro, 5-oxo-Pro-His-Pro-Gly-ProNH₂, and Phe-Pro-Leu-Pro-Ala in the presence of leucine aminopeptidase and carboxypeptidases Y and B was compared. It was found that 5-oxo-Pro-Arg-Pro was stable in the presence of the peptidases. This peptide was hydrolyzed only by carboxypeptidase Y and by ~50% over 26 h. 5-Oxo-Pro-His-Pro-Gly-ProNH₂ was stable in the presence of leucine aminopeptidase and carboxypeptidase Y whereas Phe-Pro-Leu-Pro-Ala was stable only in the presence of carboxypeptidase B. 5-Oxo-Pro-Arg-Pro was the most stable peptide in the presence of nasal mucus, blood, and the rat-brain microsomal fraction. The blood enzyme system was most effective for hydrolysis of all three peptides. Several metabolites of the aforementioned peptides were detected and identified. Conclusions about the main hydrolysis pathways of 5-oxo-Pro-His-Pro-Gly-ProNH₂ and Phe-Pro-Leu-Pro-Ala were made and suggested a set of peptides that could be formed in experiments in vivo.