The synthesis and study of simple glyprolines

Abstract

We validated the structure and performed synthesis of eight new peptides that are analogues of proglyprol, with the common formula of Pro(X)-A-Pro(Y). Here we present data on the molecular ligand-receptor activity of these peptide compounds; in particular, we present data on their ability to compete with the tripepetide Pro-Gly-Pro for specific binding sites on the plasma membranes of brain cells. The experiments were performed using a wide range of peptide concentrations, including low and ultralow, down to 10–12 mol/L. It has been shown that the peptides with substitution of the second amino acid and/or containing Ala on the C-terminus of the peptide blocked binding of tritium-labeled Pro-Gly-Pro. Regardless of the structure of the second amino acid in the composition of the modified peptide, 5-oxo-Pro-analogues induced a concentration-dependent increase in the number of binding sites of the radioactive ligand. Elongation of the peptide sequence due to addition of Ala to the C-terminus of the peptide probably increases the affinity of the analogues to the low-affinity binding sites on plasma membranes of brain cells. Taking these data into account, it is possible to consider the studied candidate peptides, i.e., synthetic modifications of the simplest glyproline, as biologically active synthetic molecules.