Igor Alexandrovich Mikhaylopulo (b. 13.08.1938, Taganrog, Rostov region, Russia), chemist. Corresponding Member of the National Academy of Sciences of Belarus (1996), Doctor of Chemical Sciences (1984), Professor (1994).
Scientific works in the field of bioorganic chemistry, biochemistry and biotechnology of nucleic acid components. Performed studies of chemical and enzymatic synthesis of modified nucleosides. He developed methods for the production of chemical compounds for the creation of antiviral and anticancer drugs, as well as for biochemical and molecular biological studies of the basics of cell functioning. He performed a series of studies on the conformational analysis of nucleosides modified by a carbohydrate moiety and a heterocyclic base, using X-ray structural analysis, NMR and KD spectroscopy. He carried out the synthesis and studied the structure/stereochemistry dependencies - a function in the series (2-5) oligoadenylates - universal mediators of the action of interferon and the related system of plants. Found that stereochemistry (2-5) oligoadenylate plays an important role in determining biological effects. Develops a technology for obtaining new effective drugs based on nucleic acid components. Under his leadership, the technology has been developed and industrial production of medicines "Tsitarabin", "Tioguanin", "Leikladin" and "Fludarabel" for the treatment of various forms of leukemia and multiple sclerosis and "Zamicit" for the treatment of AIDS has been carried out by JSC "Medications".
In the last 10 years, the scientific interests of I.A. Mikhailopulo focused on studying the mechanism of functioning of nucleoside phosphorylases (NF), the mechanisms of substrate binding and its activation in the catalytic center of these enzymes. The main goal of these studies is to study the role of structural and electronic features that determine the substrate or inhibitory activity of various compounds for the design of new, potentially biologically interesting analogues of natural nucleosides. A cascade method of converting D-pentoses into nucleosides using recombinant E. coli enzymes of ribocinase, phosphopentamutase and NF was proposed and practically implemented for the first time (in collaboration with the M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia; Academician Miroshnikov A.I.). One of the most interesting results of this period of work is the establishment of the important role of the serine-90 catalytic center of purine nucleoside phosphorylase (PNP) from E. coli in the binding and activation of a number of substrates. The possibility of the synthesis of nucleosides of 8-aza-and 8-aza-7-deazapurines was demonstrated for the first time. The results of this study are of considerable interest for the directional synthesis of new substrates and PNP inhibitors. In addition, the mechanism of functioning of uridine phosphorylase (UV) from E. coli has been studied and, using the example of PNP and UV, a methodology has been developed for analyzing enzyme-substrate interaction using semi-empirical (PM3) and quantum-chemical (ab initio) methods.
The biotechnological potential of recombinant nucleoside phosphorylases from thermophilic microorganisms was studied in comparison with E. coli enzymes and the new capabilities of the first ones as well as those immobilized on MagReSyn® carrier were demonstrated (together with the Technical University of Berlin; Prof. Dr. Peter Neubauer).
From a practical point of view, developed new chemical-enzymatic methods for the synthesis of 1) anti-leukemic compounds Fludarabine, Nelarabin and Klofarabin, as well as a number of related compounds, 2) 2-chloro-and 2-fluoro-derivatives of the nucleoside antibiotic Cordycepin against trypanosome, and 3) 8-aza-and 8-aza-7-dezapurine nucleosides for molecular biology, as well as components of oligonucleotides with a wide spectrum of biological activity (together with IBCh RAS).
Author of more than 250 scientific papers, 60 patents and copyright certificates for inventions.
State Prize of the Republic of Belarus in 2004 for the work "Chemical-Enzymatic Modification of Nucleic Acid Components and Biochemical Modification as a Scientific and Practical Basis for Searching, Creating and Manufacturing Antiviral and Antitumor Drugs". Prize of the Council of Ministers of the Latvian SSR in 1989.