SYNTHESIS OF THE TRIPEPTIDE H-ProAla-Glu-OH AND AN INVESTIGATION OF ITS TOXICOLOGICAL PROPERTIES


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Abstract

Introduction. The biological activity of peptides depends on the amino acid composition; therefore, low-molecular-weight peptides have recently occupied the most prominent place among a large number of drugs. This is attributable to the fact that amino acids are not foreign to a living organism and that they do not cause adverse reactions. The important conditions for the synthesis of peptides are the choice of side blocking groups that are easily removable, as well as that of the amino acid composition. It has been suggested that an increased number of functional groups in the structure of a dipeptide will lead to the enhanced immunobiological activity of a tripeptide. The amino acid alanine has been chosen as a bridge to extend the chain between proline and glutamic acid. Objective: to develop the most optimal scheme for the synthesis of a tripeptide with the amino acid sequence H-Pro-Ala-Glu-OH and to investigate the properties of the synthesized compound. Material and methods. A method of mixed anhydrides and activated esters was used to prepare a tripeptide. The synthesis involved three steps: the formation of the protected dipeptide Boc-Ala-Glu-(Y-Bzl)-OH, its preparation for the synthesis of a tripeptide, and per se the synthesis of the tripeptide. UV and IR spectroscopies and HPLC were employed to identify the synthesized tripeptide, the acute and chronic toxicities of which were determined. Results. The tripeptide was synthesized through peptide elongation from the C-terminus. The amino groups of the amino acids proline and alanine were protected by a tert-butyloxycarbonyl group that is better suited for the above amino acids; the Y-carbonyl group of glutamic acid was protected by a benzyl group that is easily removed by hydrogenation. The synthesized tripeptide with the amino acid sequence H-Pro-Ala-Glu-OH at a concentration of 1-10-3 mol/L was found to be a low toxic compound. Conclusion. A new low toxic tripeptide with the amino acid sequence H-Pro-Ala-Glu-OH was synthesized.

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About the authors

Natalya Dmitrievna Bunyatyan

I.M. Sechenov First Moscow State Medical University (Sechenov University); Research Center for Examination of Medical Products, Ministry of Health of the Russian Federation

Email: ndbun@mail.ru
Head of the Department of Pharmaceutical Technology and Pharmacology; chief analyst, Doctor of Pharmaceutical Sciences, Professor 8, build. 2, Trubetskaya St., Moscow 119991, Russian Federation; 8, Petrovsky Boulevard, Moscow 127051, Russian Federation

Gulomkodir Mukkamal Bobizoda

S. Aini Tajik State Pedagogical University

Email: bobievgm@rambler.ru
Professor of the Department of Organic Chemistry, Doctor of Biological Sciences, Doctor of Pharmaceutical Sciences 121, Rudaki St., Dushanbe 734003, Republic of Tajikistan

Olga Anatolyevna Popova

Research Center for Examination of Medical Products, Ministry of Health of the Russian Federation

Email: PopovaOA@expmed.ru
Head of the Laboratory of Chemical and Pharmaceutical Preparations №2 8, Petrovsky Boulevard, Moscow 127051, Russian Federation

Mikhail Mikhailovich Sapovsky

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: michael.sapovsky@mpbio.com
Professor of the Department of Pharmaceutical Technology and Pharmacology 8, build. 2, Trubetskaya St., Moscow 119991, Russian Federation

Masharif Samiev

S. Aini Tajik State Pedagogical University

Email: samievmasharif@mail.ru
Associate professor of the Department of chemistry 121, Rudaki St., Dushanbe 734003, Republic of Tajikistan

Aleksey Borisovich Prokofiev

Research Center for Examination of Medical Products, Ministry of Health of the Russian Federation; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: prokofyev56@gmail.com
Director of the Center for Clinical Pharmacology; Professor of the Department of Pharmacology and Propaedeutics of Internal Diseases 8, Petrovsky Boulevard, Moscow 127051, Russian Federation; 8, build. 2, Trubetskaya St., Moscow 119991, Russian Federation

Irina Petrovna Remezova

Pyatigorsk Medical and Pharmaceutical Institute, Branch, Volgograd State Medical University

Email: i.p.remezova@pmedpharm.ru
Professor of the Department of Toxicological and Analytical Chemistry, Doctor of Pharmaceutical Sciences 11, Kalinin Prospect, Pyatigorsk357532, Russian Federation

Vladimir Aleksandrovich Evteev

Research Center for Examination of Medical Products, Ministry of Health of the Russian Federation

Email: pharmchemist@gmail.com; evteevVA@expmed.ru
Senior Analyst of the Center for Clinical Pharmacology 8, Petrovsky Boulevard, Moscow 127051, Russian Federation

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