Synthesis and Evaluation of the Proteolytic Stability of Вос-TRP-Pro-Pro-TRP and TRP-Pro-Pro-TRP of Peptide Analogues of Pam-43 of Allosteric Modulator of Ampa Receptors

Peptides Вос-Trp-Pro-Pro-Trp and Trp-Pro-Pro-Trp were synthesized, structurally similar to PAM-43, which is a positive allosteric modulator (PAM) of AMPA receptors, the malfunction of which is considered as a symptom of many pathologies. The use of peptides synthesized from amino acids of a natural structure, unlike chemical compounds foreign to the body, as a rule, have low cytotoxicity, which allows their use in the necessary doses. It was shown that the most successful way to obtain Вос-Trp-Pro-Pro-Trp and Trp-Pro-Pro-Trp was to start synthesis by obtaining Pro-Pro, which was condensed with Вос-Trp and Trp. Their resistance to the action of peptidases has been determined. It turned out that the main way of degradation of peptides is the cleavage of the C-terminal bond of Pro-Trp with the formation of corresponding metabolites, which also degrade due to the cleavage of peptide bonds from the C-terminus of the molecule. Further studies of these peptides will make it possible to consider them as possible candidates for a new direction in the search for effective peptide analogues of PAM, with the aim of creating medicines based on them in the future.