НИИ ФХП БГУ

Research Institute for Physical Chemical Problems
of the Belarusian State University

Laboratory of biochemistry of drugs

 

 

Лаборатория биохимии 
лекарственных препаратов



The laboratory was established in 1996. The Head of the laboratory is V. Shkumatov, D.Sc, Professor, Correspondent member of the NAS of Belarus.

 

 



Directions of the research activity:

  • investigation of structure-activity relationships for peptides and proteins, using as medicines;
  • development of transgenic microorganism for purposes of directed synthesis of biologically active substances;
  • combined ultrasonic-enzymatic thrombolysis, use of enzymes in replacement therapy.
 
  
 

Main achievements:

  • enzymatic microreactors for synthesis of radioactively-Iabeled steroids have been created based on the phenomenon of «molecular
  • recognition»;
  • a new experimental-theoretical model for estimating direct and side effects of the drug compounds has been proposed based on regularities of steroids transformations in transgenic microorganisms and methods of bioinformatics;
  • enzyme activity of bacteria in relation to fluorescent analogues of cholesterol has been established, which is crucial to develop new methods for diagnostics of pathological conditions with participation of cholesterol;
  • molecular mechanisms of pulsed low- frequency ultrasonic effect on the precursor molecules and active forms of several enzymes have been discovered in the development of a new ultrasonic-enzymatic treatment of thromboembolic conditions.

 

Developments:

  • highly purified proteolytic enzymes such as a-chymotrypsin, trypsin, himopsin applyied in the isolation of racemates, resynthesis of peptide and ester bonds, chemical-enzymatic synthesis (own production);
  • recombinant microorganisms for steroid synthesis;
  • method of combined ultrasonic-enzymatic thrombolysis (in collaboration with RSPC «Cardiology» and Bellorussian Polytechnical Academy);
  • protein-vitamin supplement to compound animal and bird mixed bodder on the basis of
  • secondary products obtained in the production of biodiesel from rapeseed oil (silver medal at the Technical Fair, St. Petersburg - 2011);
  • growth supplements to microbiological culture media developed in collaboration with Co.Ltd «SIC Chimmedsynthes» (Diploma at the Technical Fair, St. Petersburg-2011);
  • series of enzymatic cleaners to remove contamination from different surfaces «Kryshtalin-F» developed in collaboration with Co.Ltd «SIC Chimmedsynthes» (silver
  • medal at the Technical Fair, St. Petersburg -2011);
  •  technology for proddction new medicinal form of the cardiac drug on the basis of phosphocreatine, kits of reagents for enzyme-linked immunosorbent assay for determination of troponins and markers ofpathology of immune and allergic disorders developed in collaboration with JV Co.Ltd «Farmlend».
 

Main publications:
 

2016 г.
  1. Harutyunyan H., Mkrtchyan V., Sukiasyan K., Sahakyan G., Poghosyan G., Soghomonyan A., Cherniavsky  E., Bondarenko E., Shkumatov V. Effect of in vivo and in vitro exposure to electrostatic field on some hematological parameters in rats // Bioelectromagnetics   2016.  Vol. 37, № 8. P.513–526 DOI: 10.1002/bem.22000  (1.583) https://www.ncbi.nlm.nih.gov/pubmed/27530776
  2. Panada J.U., Faletrov Y.V., Shkumatov V.M. Synthesis and in silico evaluation of 16β-azido pregnenolone analogue as a clickable substrate for steroidconverting enzymes // SDRP J. Comp. Chem. Mol. Model. 2016. Vol. 1. P. 1-3. (IF 1.438)http://www.openaccessjournals.siftdesk.org/articles/full-text/Synthesis-and-in-silico-evaluation.html
  3. Faletrov Y., Brzostek A., Plocinska R., Dziadek J., E. Rudaya, I. Edimecheva, V. Shkumatov Uptake and metabolism of fluorescent steroids by mycobacterial cells // Steroids. – 2016. – DOI:10.1016/j.steroids.2016.10.001 (2.513)https://www.ncbi.nlm.nih.gov/pubmed/27718364
 
2015 г.
  1. Loginova N.V., Koval’chuk T.V., Gres A.T., Osipovich N.P., Polozov G.I., HalaukoYu.S., Faletrov Y.V., Harbatsevich H.I., Hlushko A.V., Azarko I.I., BokshitsYu.V. Redox-active metal complexes of sterically hindered phenolic ligands: Antibacterial activity and reduction of cytochrome c. Part IV. Sil-ver(I) complexes with hydrazone and thiosemicarbazone derivatives of 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde // Polyhedron.  2015.  Vol. 88.  P. 125-137(IF 2.011)https://www.researchgate.net/publication/271274553_Redox-active_metal_complexes_of_sterically_hindered_phenolic_ligands_Antibacterial_activity_and_reduction_of_cytochrome_c_Part_IV_SilverI_complexes_with_hydrazone_
  2. Sluchanko N.N., Tugaeva K.V., Faletrov Y.V., Levitsky D.I. High-yield soluble expression, purification and characterization of human steroidogenic acute regulatory protein (StAR) fused to a cleava-ble Maltose-Binding Protein (MBP) // Protein Expr. Purif. 2015. Vol. 119. P.27-35(IF 1.695)https://www.ncbi.nlm.nih.gov/pubmed/26555181
  3. Sluchanko N.N., Tugaeva K.V., Faletrov Y.V., Levitsky D. High-yield soluble expression, purification and characterization of human steroidogenic acute regulatory protein (StAR) fused to a cleavable Maltose-Binding Protein (MBP) //  Protein Expr Purif. 2016 Vol. 119. P. 27-35 DOI: 10.1016/j.pep.2015.11.002.(IF 1.407)https://www.ncbi.nlm.nih.gov/pubmed/26555181


2014г.
 

  1. Revealing of novel affine interactions of NBD-labeled fluorescent steroids with bacterial steroid–converting oxidoreductases using molecular docking/ Ya.V. Faletrov, E.V. Rudaya, H.V. Hlushko, I.P. Edimecheva, V.M. Shkumatov // 50th FEBS EMBO 2014 Conference «From molecular mechanisms to Cellular Functions», 30 Aug - 4 Sep 2014, Paris, France / FEBS J. – 2014. – Vol. 281(Suppl. 1). – P. 638. 

2013г.

  1. Faletrov YV, Bialevich KI, Edimecheva IP, Kostsin DG, Rudaya EV, Slobozhanina EI, Shkumatov VM. 22-NBD-cholesterol as a novel fluorescent substrate for cholesterol-converting oxidoreductases //J. Steroid Biochem Mol Biol. – 2013. - Vol.134. – P. 59-66.
  2. Faletrov YV, Frolova NS, Hlushko HV, Rudaya EV, Edimecheva IP, Mauersberger S, Shkumatov VM. / Evaluation of fluorescent probes Nile Red and 25-NBD-cholesterol as substrates for steroid-converting oxidoreductases using pure enzymes and microorganisms.// FEBS J. – 2013. - Vol. 280 – P. 3109-3119
  3. Cherniavsky E.A., Strakha I.S., Adzerikho I.E., Shkumatov V.M. Ultrasound-assisted fibrinogen and fibrin proteolysis// Advances in Medicine and Biology, Vol.40 // Ed. L.V. Berhardt. – Nova Science Publishers, 2013. - P.281-296. (ISBN: 978-1-62100-421-9).
  4. Mauersberger S., Novikova L.A., Shkumatov V.M. Cytochrome P450 expression in Yarrowia lipolytica and its use in steroid biotransformation // Yarrowia lipolytica, Microbiology Monographs 25 // Ed. G. Barth. – Springer-Verlag Berlin Heidelberg, 2013. – P. 171-226.


2012г.
  1.  Ya.V. Faletrov, N.S. Frolova, E.V. Rudaya, D.G. Kostin, E.I. Slobozhanina, and V.M. Shkumatov 22-NBD-cholesterol, a new fluorescent substrate ofbacterial cholesterol-oxidases // Chem. Nat. Comp. – 2012. - Vol. 48, №. 1. – P. 172-173.
  2. Cherniavsky E.A., Strakha I.S., Adzerikho I.E., Shkumatov V.M. Ultrasound-assisted fibrinogen and fibrin proteolysis// Advances in Medicine and Biology, Vol.40 // Ed. L.V. Berhardt. – Nova Science Publishers, 2012. (ISBN: 978-1-62100-421-9).
  3. Cherniavsky E.A., Strakha I.S., Adzerikho I.E., Shkumatov V.M. Ultrasound-assisted fibrinogen and fibrin proteolysis// Advances in Medicine and Biology, Vol.40 // Ed. L.V. Berhardt. – Nova Science Publishers. - 2012. - P. 281-296.


2011г.

  1.  Cherniavsky E.A., Strakha I.S., Adzerikho I.E., Shkumatov V.M. Effects of low frequency ultrasound on some properties of fibrinogen and its plasminolysis // BMC Biochemistry – 2011 – 12:60.
  2. N.V. Loginova, T.V. Koval’chuk, Y.V. Faletrov, Y.S. Halauko, N.P. Osipovich, G.I. Polozov, R.A. Zheldakova, A.T. Gres, A.S. Halauko, I.I. Azarko, V.M. Shkumatov, O.I. Shadyro / Redox-active metal(II) complexes of sterically hindered phenolic ligands: Antibacterial activity and reduction of cytochrome c. Part II. Metal(II) complexes of o-diphenol derivatives of thioglycolic acid  // Polyhedron. – 2011. – V. 30. – P. 2581–2591.

2009г.
 

  1. Cherniavsky, E.A. The extraction effect of ultrasound during plasma clot disruption / Cherniavsky E.A., Adzerikho I.E., Shkumatov V.M. // Biochemistry (Moscow). Suppl. B: Biomed. Chem. – 2009. – Vol.3, № 2. – P. 164-171.
  2. L. A. Novikova, Ya. V. Faletrov, I. E. Kovaleva, S. Mauersberger, V. N. Luzikov, V. M. Shkumatov From Structure and Functions of Steroidogenic Enzymes to New Technologies of Gene Engineering // Biochemistry (Moscow). – 2009., Vol. 74, No. 13. - P. 1482-1504
  3. N. A. NemkovichYu. V. Kruchenok, A. N. Sobchuk, H. Detert, N. Wrobel, E. A. ChernyavskiĭSubnanosecond spectrofluorimetry of new indolocarbazole derivatives in solutions and protein complexes and their dipole moments // Optics and Spectroscopy. – 2009. – Vol.2. – P. 275-281


2010г.

  1.  Loginova N.V., Faletrov Y.V., Koval’chuk T.V., Osipovich N.P., Polozov G.I., Chernyavskaja A.A., Zheldakova R.A., Azarko I.I., Gres’ A.T., Shadyro O.I., Shkumatov V.M. / Redox-active metal (II) complexes of sterically hindered phenolic ligands: antibacterial activity and reduction of cytochrome c. //    Polyhedron– 2010. – V.29. -  P. 1646-1652.


2007г.

  1.  Shkumatov V.M., Usova E.V., Frolova N.S., Barth G., Mauersberger S. / Effect of steroid biosynthesis modifiers on progesterone biotransformation by recombinant yeast expressing cytochrome P450c17// Biochem. (Moscow) Suppl. Series B: Biomed. Chem. – 2007. - V.1. P. 87-94.


2006г. and earlier
 

  1. Shkumatov V.M., Radyuk V.G., Faletrov Y.V., Vinogradova A.A., Luzikov V.N., Novikova L.A. / Expression of cytochrome P450scc in Escherichia coli     cells: intracellular localization and interaction with bacterial redox proteins // Biochemistry (Mosc.) - 2006. – V.71. -  P. 884-892.
  2. V. M. Shkumatov, N. S. Frolova, E. V. Rudaya, Ya. V. Faletrov, S. Mauersberger, G. Barth / Range of substrates and steroid bioconversion reactions performed by recombinant microorganisms Saccharomyces cerevisiae and Yarrowia lipolytica expressing cytochrome P450c17// Applied Biochemistry and Microbiology – 2006. – Vol.  42 – P. 472-478 .
  3. S.L.Ovsianko, E.A.Chernyavsky, V.T.Minchenya, I.E.Adzerikho, V.M. Shkumatov /  Effect of ultrasound on activation of serine protease precursors// Ultrasonics Sonochem. – 2005. – V.12. - P. 219-223.
  4. Shkumatov V.M., Adzerikho I.E., Lesnikovich J.A., Cherniavsky E.A. Effect of ultrasound on structure and functional properties of antithrombin III and proteins of PPSB complex // Biochemistry (Mosc), 2004. V.69. P.243–250.
  5. Shkumatov V.M., Usova E.V, Radyuk V.G., Kashkan Zh.N., Kovganko N.V., Yuretzek T., Mauersberger S. Oxidation of 17alpha,20beta- and 17alpha,20alpha-dihydroxysipregn-4-en-ones--side products of biotransformation of progesterone by recombinant microorganisms expressing cytochrome P45017alpha// Bioorg Khim, 2003. V.29. P.640–647.
  6. Nazarov P.A., Drutsa V.I., Miller W.L., Shkumatov V.M., Luzikov V.N., Novikova V.A. / Formation and functioning of fused cholesterol side-chain     cleavage enzymes// DNA Cell Biol. – 2003. – V. 22. – P.243-252.
  7. Lesnikovich Iu.A., Adzerokho I.E., Shkumatov V.M. Structure-functional change in streptokinase exposed to ultrasound // Biomed Khim., 2003. V.49. P.183–190.
  8. Shkumatov V.M., Usova E.V., Poljakov Y.S., Frolova N.S., Radyuk V.G., Mauersberger S., Chernogolov A.A., Honeck H., Schunck W.-H. / Biotransformation of steroids by a recombinant yeast  strain expressing bovine cytochrome P-45017a.// Biochemistry (Mosс.) – 2002. – V. 67, P.547-560.
  9. Juvonen R.-O., Shkumatov V.M., Lang M.A. / Purification and characterization of a liver microsomal cytochrome p450 isoenzyme with a high affinity and  metabolic capacity for coumarin rfom pyrasole treated D2 mice// Eur. J. Biochem. - 1988. – V.171. – P. 205-211.
  10. Shkumatov V.M., Smettan G., Ristau O., Rein H., Ruckpaul K., Chashchin V.L., Akhrem A.A. / Quantitation of interaction between cytochrome P450scc and adrenodoxin – analysis in the median UV-region by second derivative spectroscopy// Chem-Biol. Interact. – 1988. – V.68. – P. 71-83.
  11. Shkumatov V.M., Usanov S.A., Chashchin V.L., Akhrem A.A. / Cytochrome P450 dependent pathways in corticosteroid hormone biosynthesis// Pharmazie. – 1985. – V.10. – P. 757-766.
  12. Chashchin V.L., Vasilevsky V.I., Shkumatov V.M., Akhrem A.A. / The domain structure of the cholesterol side chain cleavage cytochrome P450 from adrenocortical mitochondria// Biochem. Biophys. Acta. -1984. – V.787. – P. 27-38.
  13. Akhrem A.A., Lapko V.N., Lapko A.G., Shkumatov V.M., Chashchin V.L. / Isolation, structural organization and mechanism of action of mitochondrial     hydroxylating systems// Acta biol. Med. Germ. -1979. V.38. P.257-273.
  14. Shkumatov V.M., Usova E.V., Frolova N.S., Barth G., Mauersberger S. / Effect of steroid biosynthesis modifiers on progesterone biotransformation by recombinant yeast expressing cytochrome P450c17// Biochem. (Moscow) Suppl. Series B: Biomed. Chem. – 2007. - V.1. P. 87-94.
  15. V. M. ShkumatovN. S. FrolovaE. V. RudayaYa. V. FaletrovS. MauersbergerG. Barth / Range of substrates and steroid bioconversion reactions performed by recombinant microorganisms Saccharomyces cerevisiae and Yarrowia lipolytica expressing cytochrome P450c17// Applied Biochemistry and Microbiology – 2006. – Vol.  42 – P. 472-478 .
  16. В.М. Шкуматов, В.Г. Радюк, Я.В. Фалетров, А.А. Виноградова, Л.А. Новикова, В.Н. Лузиков. Экспрессия зрелой формы цитохрома Р450scc млекопитающих в клетках Escherichia coli: локализация и взаимодействие c электронтранспортными системами бактерий// Биохимия. 2006. Т.71. №8. С.884-92
  17. Shkumatov V.M., Radyuk V.G., Faletrov Y.V., Vinogradova A.A., Luzikov V.N., Novikova L.A. / Expression of cytochrome P450scc in Escherichia coli     cells: intracellular localization and interaction with bacterial redox proteins // Biochemistry (Mosc.) - 2006. – V.71. -  P. 884-892.
  18. ShkumatovV.M., AdzerikhoI.E., LesnikovichJ.A., CherniavskyE.A. Effect of ultrasound on structure and functional properties of antithrombin III and proteins of PPSB complex // Biochemistry (Mosc), 2004. V.69. P.243–250.
  19. Shkumatov V.M., Usova E.V, Radyuk V.G., Kashkan Zh.N., Kovganko N.V., Yuretzek T., Mauersberger S. Oxidation of 17alpha,20beta- and 17alpha,20alpha-dihydroxysipregn-4-en-ones--side products of biotransformation of progesterone by recombinant microorganisms expressing cytochrome P45017alpha// Bioorg Khim, 2003. V.29. P.640–647.
  20. LesnikovichIu.A., AdzerokhoI.E., ShkumatovV.MStructure-functional change in streptokinase exposed to ultrasound // Biomed Khim., 2003. V.49. P.183–190.
  21. Shkumatov V.M., Usova E.V., Poljakov Y.S., Frolova N.S., Radyuk V.G., Mauersberger S., Chernogolov A.A., Honeck H., Schunck W.-H. / Biotransformation of steroids by a recombinant yeast  strain expressing bovine cytochrome P-45017a.// Biochemistry (Mosс.) – 2002. – V. 67, P.547-560.
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