Baku, Azerbaijan
As peptides, which by their nootropic and neuroprotective activity would not be inferior to Semax, different fragments of ACTH were tested: ACTH-(7-10)-PGP, ACTH-(4-10)-PGP, ACTH-(6-10)-PGP, ACTH-(5-7)-PGP. The animal experiments have shown that ACTH-(6-9)-PGP has proven to be particularly successful in terms of biological properties. This peptide not only showed nootropic and anxiolytic activity, but also increased the viability of cultured glial cells obtained from the cerebral cortex of rats with ischemic brain damage. When studying the effect of ACTH-(4-10)-PGP on the size of the necrotic focus in rats, it turned out that this peptide, like Semax, reduces the size of necrosis during the development of ischemic stroke in rats by approximately 50%. All these drugs are planned to be used as medicines. With different ways of introducing the original peptides, a different set of hydrolysis products is formed, while it is known that the resulting shorter peptides often have their own biological activity. To find the spatial structure of this peptide molecule, we used the theoretical conformational analysis method, which allows us to calculate the three-dimensional structure of biomolecules based on the known amino acid sequence. The calculation was carried out within the framework of the mechanical model of molecules, taking into account the non-valent, electrostatic, torsion interactions and the energy of hydrogen bonds. The non-valent interactions were assessed by Lennard-Jones potential. Electrostatic interactions were calculated in a monopole approximation according to the Coulomb law using partial charges on atoms. The conformational capabilities of this molecule are studied under the conditions of the water environment, in connection with which the value of the dielectric constant is assumed to be 10. The energy of hydrogen bonds was estimated using Morse potential. The spatial structure of the ACTH-(4-10)-PGP molecule (Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Pro-Gly-Pro) has been studied fragmentarily. At the first stage, the conformational capabilities of the N-terminal tripeptide fragment Met4-Glu5-His6 and the C-terminal heptapeptide fragment Phe7-Arg8-Trp9-Gly10-Pro-Gly-Pro were studied. The calculation showed that there is a strong energy differentiation between the forms of the main chain. The conformations of 11 forms of the main chain fall into a wide energy range of 0-15 kcal/mol. It is shown that the spatial structure of the heptapeptide molecule can be represented by eleven low-energy forms of the main chain. The low-energy conformations of the molecule, the values of the dihedral angles of the main and side chains of amino acid residues are found, the energy of intra-and inter-residual interactions is estimated.
ACTH-(4-10)-PGP, theoretical conformational analysis, spatial structure, conformation
1. Shevchenko K.V., Dulov S.A., Andreeva L.A., Nagaev I.Yu., Shevchenko V.P., Radilov A.S., Myasoedov N.F. Ustoychivrst' His-Phe-Arg-Trp-Pro-Gly-Pro k deystviyu leycinaminopeptidazy, karboksioeotidahy Y i fermentnym sistemam nazal'noy slizi, krovi i plazmy krovi krys. Bioorganicheskaya himiya, 2016, t. 42, № 2, s. 171-181. [ Shevchenko K.V., Dulov S., Andreeva L.A., Nagaev I.Yu., Shevchenko V.P., Radilov A.S., Myasoedov N.F. Stability of His-Phe-Arg-Trp-Pro-Gly-Pro to Leucine Aminopeptidase, Carboxypeptidase Y, Nasal Slime, Blood and Plasma of Rats. Journal of Bioorganic Chemistry, 2016, vol. 42, no. 2, pp. 171-181. (In Russ.)]
2. Akhmedov N.A., Tagiyev Z.H., Hasanov E.M., Akverdieva G.A.Theoretical conformational analisis of the bovine adrenal medulla 12 residue peptide molecule. J. Molecular Structure, 2003, vol. 646, pp.75-80.
3. Akhmedov N.A., Ismailova L.I., Agayeva L.N., Gocayev N.M. The spatial structure of the cardio active peptides. Peptid and Protein Research, 2010, vol. 11, pp. 87-93.
4. Gadzhieva Sh.N., Ahmedov N.A., Masimov E.A, Godzhaev N.M. Prostranstvennaya struktura molekuly Thr-Pro-Ala-Glu-Asp-Phe-Met-Arg-Phe-NH2 Biofizika, 2013, t. 58, vyp. 4, s. 587-590. [Gadjieva Sh.N., Akhmedov N.A., Masimov E.A., Godjaev N.M. Spatial Structure of Thr-Pro-Ala-Glu-Asp-Phe-Met-Arg-Phe-NH2. Biophysics, 2013, vol. 58, pp. 587-590 (In Russ.)]
5. Akverdieva G.A, Akhmedov N.A., Godjayev N.M. Insights into bioactive conformation of melanotropins. AJP, Fizika, 2017, vol. 22, no. 4, Section: En, pp. 6-12.
6. Hasanov E.M., Akhmedov N.A. Spatial Structure of Peptide BAM-20P. International Journal of Innovative Science and Research Technology, 2018, vol.3, iss. 3, pp. 72-76.
7. IUPAC-IUB, Quantiby, Units and Sybbols in Physical Chemistry. Blackwell Scientific Publications, 1988, vol. 39.
