Group of Molecular Pharmacology

Head

Zenoviy Yu. Tkachuk

Ph.D. (Mol. Biol.), Senior Staff Scientist
Phone: (380-44) 526-20-16
Fax: (380-44) 526-07-59;
E-mail: ztkachuk@yahoo.com; ztkachuk@bigmir.net

Education and Degrees:

19651970 Graduate Student, Faculty of Biology, Yurii Fedkovych Chernivtsi National University, Chernivtsi, Ukraine, M.Sc. (biochemistry)

19711973 Postgraduate Student, Department of Genetics of Microorganisms, D. K. Zabolotny Institute of Microbiology and Virology (IMV), NASU, Kyiv, Ukraine

1974 Ph.D. (genetics of microorganisms)

Professional Employment:

19741977 Junior Research Scientist, Department of Genetics of Microorganisms, IMV NASU, Kyiv, Ukraine

19771983 Junior Research Scientist, Institute of Molecular Biology and Genetics (IMBG), NASU, Kyiv, Ukraine

19831987 Senior Research Scientist, IMBG NASU, Kyiv, Ukraine

19871998 Head of the Laboratory of Oligonucleotides Biochemistry, IMBG NASU, Kyiv, Ukraine

since 2004 Head of the Laboratory of Molecular Pharmacology, IMBG NASU, Kyiv, Ukraine

19911992 Advisor to the Verhovna Rada of Ukraine

19921993 Advisor to the Prime-minister of Ukraine

19931994 Advisor to the President of Ukraine

19951996 Advisor to the Speaker of Ukraine

19961997 Advisor to the Prime-minister of Ukraine

Research Area:

Studying the mechanism of action of 2-5oligoadenylates and their role in the regulation of the innate immunity

Creating new immunomodulatory and antiviral drugs from natural oligonucleotides

urrent Research Activities and Recent Achievements:

We study the immunomodulatory effects and antiviral activity of oligoadenilates against a wide range of viruses of both DNA and RNA nature. We also investigate the effect of oligonucleotides on innate immunity genes expression at various viral diseases and cancer.
Fig. 1. Structures of 2-5- oligoadenylate and its analogues, that were synthesized by phosphotriester method
We examine the polyvalent activity of oligoadenilates and their ability to bind signaling proteins, slightly altering their conformation and thus modulating their activity. These are primarily Ca2+ binding proteins, protein kinases and nucleases. The ability of oligonucleotides to change the secondary structure of both viral DNA and RNA, making them accessible for enzymatic cleavage is studied.
Fig. 2. MALDI mass spectrum of interferon and 3-5oligoadenylate. It was shown that all investigated oligoadenylates, regardless of their length and structural features, are capable of multiple interactions with α-interferon
The hypothesis which explains the mechanism of action of oligoadenylates and their involvement in the regulation of innate immunity has been proposed. Based on this hypothesis, a new imunomodulating drug Nucleinat and antiviral medicine Nuclex with a wide spectrum of action have been developed and implemented. Nuclex is effective against different viruses of both RNA and DNA nature.
Fig. 3. Multy antiviral drug Nuclex. Indications for use. As the drug in the antiinfluenza and flu therapy. In complex therapy of the chronic virus hepatitis, urogenital herpes. Order of the Ministry of Health of Ukraine 01.09.10 No. 752

National Grants:

Projects of National Academy of Sciences of Ukraine:

  • 20132014 Project Fundamentals of the development of anticancer and antiviral drugs (scientific supervisors Dubey I. Ya., Tkachuk Z. Yu.)
  • 20092013 Project To study the mechanism of 2, 5-oligoadenylate interaction with calcium-binding proteins (scientific supervisor Tkachuk Z. Yu.)
  • 20072010 Project To study the mechanism of calmodulin activation of core 2-5-oligoadenylates and their analogues and the synthesis and study of biological activity of new ligands based on oligonucleotides (scientific supervisor Tkachuk Z. Yu.)
  • 20042008 Project To study the interaction of 2-5-oligoadenylate analogues with fosfodiesterase of cyclic nucleotides and to monitor new anti-inflammatory drugs in vitro and in vivo (scientific supervisors Tkachuk Z. Yu., Dubey I. Ya.).

Collaboration:

with Ukrainian organizations:

  • Taras Shevchenko National University of Kyiv (Kyiv)
  • Institute of Physics, NASU (Kyiv)
  • O. V. Palladin Institute of Biochemistry, NASU (Kyiv)

with foreign organizations:

  • Institute of Biochemistry and Biophysics, PAS (Warsaw, Poland).

Selected publications:

  1. M.M. Vivcharyk, O.O. Ilchenko, S.M. Levchenko, Z.Yu. Tkachuk. RNA Complex with mannitol, its spectral characteristics and biological activity. Reports of the National Academy of Sciences of Ukraine, 2016, 10: 78-83.
  2. Melnichuk N., Vivcharyk M., Tkachuk Z. Effect of Oligoribonucleotides-D-mannitol complex on the hemagglutinin of influenza A (H1N1) virus. 8th International conference bioresources and viruses, 12-14th September 2016, Kyiv, Ukraine. 2016. Abstract P. 45-46.
  3. Shmarakov IO, Marchyshak TV, Borschovetska VL, Marchenko MM, Tkachuk ZYu. Hepatoprotective activity of exogenous RNA. Ukr. Biochem. J. 2015; 87(4):37-44.
  4. Chernega OI, Levchenko SM. Nature of the lowest electronic transition of thia- and quino-cianines with fluori-nated polimethine chaine. Dyes and Pigments. 2015; 123:176-185.
  5. Tkachuk Z. Multiantivirus compo-und, composition and method for treatment of virus disease. US patent. 2014;#8,722,642 B2:61.
  6. Tkachuk ZYu, Kozlov AV, Skorobogatov OYu. Structural Changes In Therapeutic RNAs. Macromolecular Symposia. 2014;335:17-19.
  7. Levchenko SM, Rebriev AV, Tkachuk VV, et al. The detection of interaction betwe-en oligonucleotides and interferon, a key protein of antiviral cell defense system. Mol.Cryst.Liq.Cryst. 2014;590(1):213-220.
  8. Viniychuk OO, Levchenko SM, Przhonska OV, et al. Electronic transition in polymerthine dyes involving local and delocalized levels. Jour.Mol.Str. 2014;1060:30-37.
  9. Bashmakova N, Shaydyuk E, Levchenko S, et al. Desigh and electronic structure of new styryl dye bases: steady-state and time resolved spectrosco-pic studies. Journal of Physical Chemistry A. 2014;118(25):4502-4509.
  10. Skorobogatov O, Lozhko D, Zhukov I, et al. Impact of dephos-phorylated 2'-5'-linked oligoade-nylates on apo-S100A1 proteins conformation, studied by hetero-nuclear NMR and circular dichroism. Biopolym. Cell. 2014;30:279-285.
  11. Tkachuk ZYu. 2'5'Oligoadenylates as a "tool" of innate immunity. Biopolym. Cell. 2013; 29(4):26676. doi:10.7124/bc.000821
  12. Levchenko SM, Rebriev AV, Tkachuk VV, Dubey LV, Dubey IYa, Tkachuk ZYu. Studies on the interaction of oligoadenylates with proteins by MALDITOF mass spectrometry. Biopolym. Cell. 2013; 29(1):428. doi: 10.7124/bc.000804
  13. Tkachuk Z. Multiantivirus compound, composition and method for treatment of virus disease. United States Patent 2013 N 8,420,617 B2. Apr.16, P. 38.
  14. Tkachuk ZYu, Sotska YaA, Frolov VM, Kruglova OA. Nuclex therapy for patients with chronic hepatitis C. Int. J. Immunological Studies. 2012; 1(4):34964. doi:10.1504/IJIS.2012.051236
  15. Frolov VM, Tkachuk ZYu, Kruglova OA. Application of immuno modulator Nucleinat in clinical practice Infections Diseases. 2012. 4:8290.
  16. Tkachuk ZYu, Dubey L, Tkachuk VV, et al. Studying the interaction of 2'5'oligoadenylate and their counterparts from proteins by fluorescence spectroscopy. Ukr.biohim.Zh. 2011; 83(1):4553.
  17. Tkachuk Z. Compound, compozision and method for treatment of inflammatory and inflammatoryrelated disorders. United States Patent2004 N US 6,737,271. May 18, P.38.