[Effect of modification of the N-terminal region of molecule on the expression of neotropic effect of semax analogues].

A comparative study of neotropic activity of semax (MEHFPGP), an analogue of the ACTH(4-10), and some of its derivatives in which the N-terminal methionine was modified or substituted with other amino acid residues was performed. The effect of these peptides on learning of albino rats in tests with positive (alimentary) and negative (pain) reinforcement was studied. In the case of modification of methionine by attachment of the gluconic-acid residue or substitution of methionine with lysine, the neotropic effect of the peptide was retained. The substitution of methionine with tryptophan or serine resulted in a decrease in the neotropic activity. The substitution of methionine with glycine, threonine, or alanine caused a complete loss of the neotropic activity of the peptide. Therefore, the amino acid residue located at position 1 of the heptapeptide analogue semax, plays a key role in retaining the neotropic effects of the peptide and determines the degree of their expression.