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The study of the effects of adrenocorticotropic hormone (ACTH) fragments (neuropeptides), particularly the 4-10 fragment (ACTH(4-10)), began in the 1960s and 1970s. At that time, it was demonstrated that these short peptides, especially those containing 7 amino acids, ACTH(4-10), could stimulate learning in white rats without exhibiting hormonal activity. However, due to the instability of such a peptide in the body, its practical use in medicine was impossible.
In the late 1970s, the Ministry of Defense and the Academy of Medical Sciences of the USSR set the task of developing promising nootropic drugs, with a focus on the minimal active fragment of ACTH(4-7).
To create a prolonged-release form of the peptide, they utilized the fact that most exo- and endopeptidases with low specificity do not cleave sequences enriched with proline residues. Specific proline hydrolases, unlike the former, are present in small quantities.
Based on this, a series of analogs were synthesized with regions enriched with proline residues at the end of the peptide molecule. It turned out that the analog containing the C-terminal tripeptide Pro-Gly-Pro led to both the greatest enhancement of the effect and its prolongation. The duration of action of such a peptide was 50 times longer than that of natural ACTH(4-10). This sequence was chosen for the creation of a drug called "Semax" (seven amino acids).
A little bit of medicine.