Shevchenko Konstantin Valeryevich | Institute of Molecular Genetics
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Academic degree:
Doctor of Philosophy (Chemistry)
Academic title:
without academic rank
Division of IMG:
Sector of regulatory peptides
Position:
Researcher
Telephone:
+7-499-196-02-16
Е-mail: |
Main research interests
Investigation of novel nootropic preparations by incorporation of new fragments in peptides has been the principal direction of research. The resistance of the preparation Semax (Sem) to the action of amino peptidases after the replacement of its N-end Met by Ala, Gly, Thr and Trp was studied. Ala-Sem, Gly-Sem and Thr-Sem (Semax analogues) were shown to be more resistant to proteolysis as compared with Semax. With the same approaches used, the new promising peptide ACTG (6-9)PGR (His-Phe-Arg-Trp-Pro-Gly-Pro) different from Semax by its amino acid composition (Met-Glu-His-Phe-Pro-Gly-Pro) was produced. The bioavailability parameters of nasally introduced ACTG (6-9)PGR were higher, an indication to good prospects for the intranasal drug delivery in clinical practice.
Another direction in the pursuit of biologically active peptides was the search for short peptides with medicinal properties. The relevance of such an approach was demonstrated in studies of the in vitro proteolysis of Pro-Gly-Pro-Leu, Pro-Gly-Pro-Gly and Pro-Gly-Pro. These peptides were shown to be considerably more resistant than Semax to the action of N-leucine aminopeptidase as well as to nasal mucus enzymes and the microsomal fraction of rat brain and blood. The composition of the metabolites produced in the proteolysis of these peptides was also analyzed. In vivo studying of the intranasal and intravenous introduction of the tetrapeptide Pro-Gly-Pro-Leu allowed its maximal amount and that of its degradation products to be determined in the brain and its parts. Based on the data yielded, contribution of some or other metabolic path of Pro-Gly-Pro-Leu was assessed. The amount of metabolites in the blood showed that the degradation of the nasally introduced peptide from the N-end was more effective at the first stage of Pro-Gly-Pro-Leu proteolysis. The percentage of direct drug transport from the nasal cavity into the rat brain after intranasal introduction of Pro-Gly-Pro-Leu was counted (30%). Receptor binding of peptides in rat brain parts was studied parallel to their stability and degradation direction. Similar parallel comparisons help explain the particular features of different peptides’ effect on cellular responses.
Another direction in the pursuit of biologically active peptides was the search for short peptides with medicinal properties. The relevance of such an approach was demonstrated in studies of the in vitro proteolysis of Pro-Gly-Pro-Leu, Pro-Gly-Pro-Gly and Pro-Gly-Pro. These peptides were shown to be considerably more resistant than Semax to the action of N-leucine aminopeptidase as well as to nasal mucus enzymes and the microsomal fraction of rat brain and blood. The composition of the metabolites produced in the proteolysis of these peptides was also analyzed. In vivo studying of the intranasal and intravenous introduction of the tetrapeptide Pro-Gly-Pro-Leu allowed its maximal amount and that of its degradation products to be determined in the brain and its parts. Based on the data yielded, contribution of some or other metabolic path of Pro-Gly-Pro-Leu was assessed. The amount of metabolites in the blood showed that the degradation of the nasally introduced peptide from the N-end was more effective at the first stage of Pro-Gly-Pro-Leu proteolysis. The percentage of direct drug transport from the nasal cavity into the rat brain after intranasal introduction of Pro-Gly-Pro-Leu was counted (30%). Receptor binding of peptides in rat brain parts was studied parallel to their stability and degradation direction. Similar parallel comparisons help explain the particular features of different peptides’ effect on cellular responses.
Awards, achievements, memberships
2006 – First Degree Diploma for the best article of 2006 V.V.Bezuglov, N.M.Gretskaya, A.V.Blazhenova, E.L.Andrianova, M.G.Akimov, M.Yu.Bobrov, I.V.Nazimov, M.A.Kisel’, O.L.Sharko, A.V.Novikov, N.V.Krasnov, V.P.Shevchenko, K.V.Shevchenko, T.V.Vyunova, N.F.Myasoedov “Arachidonoyl amino acids and arachidonoyl peptides: Synthesis and properties” //Russian Journal of Bioorganic Chemistry. 2006. Vol.32. Issue 3. P.231-239. DOI: 10.1134/S1068162006030046.
2009 – Prize Winner Diploma # 40 of 2009 of the International Academic Publishing Company “Nauka/Interperiodica” for the best publication in the Publishers’ Journals K.V.Shevchenko, A.P.Khrapko, V.I.Schwets, N.F.Myasoyedov “The use of phospholipid nanoparticles for increasing Semax resistance in various proteolytic biological media” //Doklady Biological Sciences. 2009. Vol.429. Issue 1. P.505-507. DOI: 10.1134/S0012496609060076.
2009 – Prize Winner Diploma # 40 of 2009 of the International Academic Publishing Company “Nauka/Interperiodica” for the best publication in the Publishers’ Journals K.V.Shevchenko, A.P.Khrapko, V.I.Schwets, N.F.Myasoyedov “The use of phospholipid nanoparticles for increasing Semax resistance in various proteolytic biological media” //Doklady Biological Sciences. 2009. Vol.429. Issue 1. P.505-507. DOI: 10.1134/S0012496609060076.
Publications
In 2008 through 2015, 31 articles and 40 abstracts were published, 6 patents granted.
The most significant publications of 2008 – 2015:
Papers:
The most significant publications of 2008 – 2015:
Papers:
- T.V.Vyunova, L.A.Andreeva, K.V.Shevchenko, V.P.Shevchenko, M.Yu.Bobrov, V.V.Bezuglov, N.F.Myasoedov “Binding of tripeptide Pro-Gly-Pro labeled at the C-terminal proline residue to plasma membranes of the rat forebrain” //Doklady Biological Sciences. 2008. Vol.419. Issue 1. P.95-96. DOI: 10.1134/S0012496608020075.
- K.V.Shevchenko, A.P.Khrapko, V.I.Schwets, N.F.Myasoyedov “The use of phospholipid nanoparticles for increasing Semax resistance in various proteolytic biological media” //Doklady Biological Sciences. 2009. Vol.429. Issue 1. P.505-507. DOI: 10.1134/S0012496609060076.
- T.V.Vyunova, K.V.Shevchenko, V.P.Shevchenko, V.V.Bezuglov, N.F.Myasoedov “A biotechnological procedure for preparing short peptides and their radioactively labeled analogs for estimating specific binding of Semax and its metabolites in various sections of rat brain” //Radiochemistry. 2009. Vol.51. Issue 2. P.183-189. DOI: 10.1134/S1066362209020167.
- T.V.Vyunova, L.A.Andreeva, K.V.Shevchenko, N.F.Myasoedov “Some key moments of synthetic neuropeptides analogues biological activity molecular mechanism” //FEBS Journal. 2011. Vol.278. p.278. Supplement 1. Special Issue: SI. 36th FEBS Congress of the Biochemistry for Tomorrows Medicine. Torino. Italy. JUN 25-30. 2011.
- K.V.Shevchenko, T.V.Vyunova, I.Yu.Nagaev, L.A.Andreeva, L.Yu.Alfeeva, N.F.Myasoedov “Studies of the aminopeptidase proteolysis of semax analogues with different N-terminal amino acid residues” //Russian Journal of Bioorganic Chemistry. 2011. Vol.37. Issue 4. P.421-427. DOI: 10.1134/S1068162011040133.
- K.V.Shevchenko, T.V.Vyunova, I.Yu.Nagaev, L.A.Andreeva, N.F.Myasoedov “Proteolysis of simple glyprolines by leucine aminopeptidase and enzymes from nasal mucus, brain membranes, and blood of rats” //Russian Journal of Bioorganic Chemistry. 2013. Vol.39. Issue 3. P.283-287. DOI: 10.1134/S1068162013030151.
- K.V.Shevchenko, I.Yu.Nagaev, L.A.Andreeva, V.P.Shevchenko, N.F.Myasoedov “Stability of Semax acetyl to proteolysis in various biological media” //Doklady Biological Sciences. 2013. Vol.449. Issue 1. P.110-112. DOI: 10.1134/S0012496613020166.
- K.V.Shevchenko, I.Yu.Nagaev, L.A.Andreeva, L.Yu.Alfeeva, N.F.Myasoedov “Study of proteolysis of semax analogues with different N-terminal amino acids by carboxypeptidases” //Doklady Biological Sciences. 2013. Vol.450. Issue 1. P.146-148. DOI: 10.1134/S0012496613030101.
- V.P.Shevchenko, I.Yu.Nagaev, K.V.Shevchenko, N.F.Myasoedov “Specific features of deuterium and tritium labeling of Pro-Gly-Pro-Leu and of physiologically active amino acids” //Radiochemistry. 2013. Vol.55. Issue 3. P.346-351. DOI: 10.1134/S1066362213030181.
- T.V.Vyunova, L.A.Andreeva, K.V.Shevchenko, N.F.Myasoedov “The molecular aspects of peptide regulation of Glutamate and GABA-ergic receptor systems functional activity” //FEBS Journal. 2014. Vol.281. P.385-386. Supplement 1. Special Issue: SI. FEBS EMBO. Paris. 30 August 2014 - 4 September 2014.
- K.V.Shevchenko, T.V.Vyunova, L.A.Andreeva, I.Yu.Nagaev, V.P.Shevchenko, N.F.Myasoedov “Proteolysis of Pro-Gly-Pro-Leu in the hippocampus, cerebellum, and cerebral cortex in rats after intravenous injection” //Bulletin of Experimental Biology and Medicine. 2014. Vol.158. Issue 1. P.37-41. DOI: 10.1007/s10517-014-2686-7.
- T.V.Vyunova, L.A.Andreeva, K.V.Shevchenko, V.P.Shevchenko, M.Yu.Bobrov, V.V.Bezuglov, N.F.Myasoedov “Characteristic features of specific binding of pentapeptide HFPGP labeled at the C-terminal proline residue to rat forebrain plasma membranes” //Doklady Biochemistry and Biophysics. 2014. Vol.456. Issue 1. P.101-103. DOI: 10.1134/S1607672914030077.
- K.V.Shevchenko, T.V.Vyunova, L.A.Andreeva, I.Yu.Nagaev, V.P.Shevchenko, N.F.Myasoedov “Comparison of pharmacokinetics and metabolism of Pro-Gly-Pro-Leu administered intranasally and intravenously in the blood and brain of rats” //Doklady Biochemistry and Biophysics. 2014. Vol.456. Issue 1. P.111-115. DOI: 10.1134/S1607672914030090.
- K.V.Shevchenko, I.Yu.Nagaev, V.N.Babakov, L.A.Andreeva, V.P.Shevchenko, A.S.Radilov, N.F.Myasoedov “Proteolysis of His-Phe-Arg-Trp-Pro-Gly-Pro in the blood and brain of rats in vivo” //Doklady Biochemistry and Biophysics. 2015. Vol.464. Issue 1. P.301-304. DOI: 10.1134/S1607672915050087.
- K.V.Shevchenko, T.V.Vyunova, A.S.Radilov, L.A.Andreeva, I.Yu.Nagaev, V.P.Shevchenko, V.R.Rembovsky , N.F.Myasoedov “Penetration of thyroliberin in the blood and brain regions at intranasal or intravenous administration” //Doklady Biochemistry and Biophysics. 2015. Vol.465. Issue 1. p.436-439. DOI: 10.1134/S1607672915060228.
- V.P.Shevchenko, A.S.Radilov, I.Yu.Nagaev, К.V.Shevchenko, V.R.Rembovskii, N.F.Myasoedov “Influence of the conditions of deuterium and tritium labeling of His-Phe-Arg-Trp-Pro-Gly-Pro oligopeptide on the isotope exchange efficiency” //Radiochemistry. 2015. Vol.57. Issue 5. P.542-545. DOI: 10.1134/S1066362215050161.
- K.V.Shevchenko, T.V.Vyunova, L.A.Andreeva, I.Yu.Nagaev, V.P.Shevchenko, N.F.Myasoedov “Proteolysis of Pro-Gly-Pro-Leu in rat-brain hippocampus, cerebellum, and cortex upon intranasal administration” //Pharmaceutical Chemistry Journal. 2015. Vol.49. Issue 2. P.82-87. DOI: 10.1007/s11094-015-1226-8.