Laboratory of Organic Synthesis

Vladimir N. Silnikov,
D.Chem.Sci.Laureate of the Lenin’s Komsomol Prize
Phone: +7(383)363-51-82
Email

• Design and development of synthetic approaches to prepare reagents to be used as tools for molecular biology studies, including modified nucleosides, nucleoside triphosphates and nucleic acids.
• Design and synthesis of artificial ribonucleases – low-molecular catalysis of RNA degradation.
• Development of compounds with antiviral and antibacterial properties on the basis of artificial ribonucleases.

• The approaches to design of low-molecular catalysts for RNA phosphodiester bonds degradation have been developed. The basis of these approaches is to conjugate organic molecules that model the fragments of catalytic centers of natural nucleolytic enzymes with the structures that have the affinity to nucleic acids.
• New methods for the synthesis of oligonucleotide conjugates with a wide range of compounds that bear aliphatic amino groups have been developed. Based on this approach, a number of oligonucleotide conjugates bearing RNA-hydrolyzing catalytic centers, photoactive and fluorescent groups were synthesized. [Mitrofanov D.V. et al., Genetika. 2008. 44, 1684; Koroleva L.S. et al., Protein & Peptide Letters. 2007. 14, 151].
• Design and synthesis of new analogs of nucleic acids and terminating triphosphates based on morpholino nucleosides have been carried out. [Abramova T.V. et al., Indian J. Chem. 2009. 48B, 1721; Patent RF N.2326888, 2006; Abramova T.V. et al., Bioorg. Med. Chem. 2008. 16, 9127].
• A number of antiviral and antibacterial compounds with a wide spectrum of activities for veterinary and medicine have been developed. These compounds are currently at different stages of testing. [Patents RF: N.2443705, 2012; N.2402563, 2010; N.2399669, 2010; N.2399388, 2010].
• A number of artificial ribonucleases with high antiviral and antibacterial activity have been suggested. [Goncharova E.P. et al., Dokl. Biochem. Biophys. 2009. 427, 221; Fedorova A.A. et al., Antivir Res. 2011. 91(3), 267].
• A new nanocomposite system on the base of SiO2 nanoparticulars for delivery of nucleoside triphosphates analogues into cells was developed. A new type of linker groups for the modification of pyrimidine nucleosides was developed. [Vasilyeva S.V. et al., Nucleos. Nucleot. & Nucl. Acids. 2011. 30(10), 753; Vasilyeva S.V. et al., Bioorg. Med. Chem. 2013. 21(3), 703].

1. Abramova T.V., Morozova O.B., Sil’nikov V.N., Yurkovskaya A.V. Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach. Beilstein J. Org Chem. 2013. 9, 2898–2909.
2. Burakova E.A. Artificial ribonuclease based on DABCO: design and synthesis (monograph). Constructing and synthesis. LAP LAMBERT Academic publishing, 2013. 136 pages.
3. Morozova O.B., Yurkovskaya A.V., Kiryutin S.A., Yarinich L.A., Sil’nikov V.N., Sagdeev R.Z. Influence of charge on the amino group on the speed and direction of intramolecular electron transfer in oxidized short peptides containing tryptophan and tyrosine. Doklady Akademii nauk, 2013. 452 (4), 412-418.
4. Kupryushkin M.S., Konevetz D.A., Vasilyeva S.V., Kuznetsova A.S., Stetsenko D.A., Pyshnyi D.V. Oligonucleotide Functionalization by a Novel Alkyne-Modified Nonnucleosidic Reagent Obtained by Versatile Building Block Chemistry. Nucleosides Nucleotides Nucleic Acids. 2013. 32(6), 306-319.
5. Davydova A.S., Vorobjeva M.A., Zenkova M.A., Sil’nikov V.N., François J.C., Venyaminova A.G. New cellular RNA elimination method for cell-based SELEX of modified RNA aptamers. Mol. Biol. (Rus.). 2013. 47 (6), 904-906.
6. Evdokimov A.N., Petruseva I.O., Tsidulko А.Yu., Koroleva L.S., Serpokrylova I.Y., Silnikov V.N., Lavrik O.I. New synthetic substrates of mammalian nucleotide excision repair system. Nucleic Acids Res. 2013. 41(12), e123.
7. Godovikova T.S., Lisitsky V.A., Antonova N.M., Popova T.V., Zakharova O.D., Chubarov A.S., Koptyug I.V., Sagdeev R.Z., Kaptein R., Akulov A.E., Kaledin V., Nikolin V.P., Baiborodin S.I., Koroleva L.S., Silnikov V.N. Ligand-directed Acid-sensitive Amidophosphate 5-Trifluoromethil-2'-deoxyuridine Conjugate as a Potential Theranostic Agent. Bioconjugate Chem. 2013. 15(24-5), 780-795.
8. Niittymaki Teija, Burakova E.A., Laitinen Evelina, Leisvuori Anna, Virta Pasi, Lonnberg Harri. Zn2+ Complexes of 3,5-bis[1,5,9-triazacyclododecan-3-yloxy)methyl]phenyl conjugates of oligonucleotides as artificial RNases: the effect of oligonucleotide conjugation on uridine selectevity of cleaving agent. Helvetica Chim. Acta. 2013. 96(1), 31-43.
9. Abramova T.V. Frontiers and Approaches to Chemical Synthesis of Oligodeoxyribonucleotides. Molecules. 2013. 18, 1063-1075.
10. Vasilyeva S.V., Sil’nikov V.N., Shatskaya N.V., Levina A.S., Repkova M.N., Zarytova V.F. SiO2 Nanoparticles as platform for delivery of nucleoside triphosphates analogues into cells. Bioorg. Med. Chem. 2013. 21(3), 703-711.
11. Grin I.R., Vasilyeva S.V., Dovgerd A.P., Sil’nikov V.N., Zharkov D.O. Human and bacterial DNA polymerases discriminate against 8-oxo-2'-deoxyadenosine- 5'-triphosphate. Biopolymers & Cell. 2012. 28(4), 306-309.
12. Vasilyeva S.V., Budilkin B.I, Konevetz D.A., Sil’nikov V.N. Synthesis of novel nucleoside 5'-triphosphates and phosphoramidites containing alkyne or amino groups for the postsynthetic functionalization of nucleic acids. Nucleos. Nucleot. & Nucl. Acids. 2011. 30(10), 753-767.
13. Abramova T.V., Sil’nikov V.N. Synthesis and properties of carbohydrate-phosphate backbone-nodified oligonucleotide analog and nucleic acid mimetics. Russian Chemical Reviews. 2011. 80, 429-453.
14. Kasakin M.F., Abramova T.V., Sil’nikov V.N. Synthesis of 2’-aminomethylmorpholino nucleoside analogues containing the 4’-carboxymethyl linker group. Russian J. Bioorganic Chemistry. 2011. 37(6), 752-757.
15. Gulevich A.V., Koroleva L.S., Morozova O.V., Bakhvalova V.N., Sil’nikov V.N., Nenajdenko V.G. Multicomponent Synthesis of Artificial Nucleases and their RNase and DNase activity. Beilstein J. Org. Chem. 2011. 7, 1135-1140.
16. Beloglazova N.G., Fabani M.M., Polushin N.N., Sil’nikov V.N., Vlassov V.V., Bichenkova E.V., Zenkova M.A. Site-selective artificial ribonucleases: oligonucleotide conjugates containing multiple imidazole residues in the catalytic domain. J. Nucleic Acids. 2011. e748632.
17. Fedorova A.A., Azzami K., Ryabchikova E.I., Spitsyna Y.E., Silnikov V.N., Ritter W., Gross H.J., Tautz J., Vlassov V.V., Beier H., Zenkova M.A. Inactivation of a non-enveloped RNA virus by artificial ribonucleases: Honey bees and Acute bee paralysis virus as a new experimental model for in vivo antiviral activity assessment. Antiviral Research. 2011. 91(3), 267-277.

1. Evdokimov A.N., Petruseva I.O., Tsidulko A.Ju., Koroleva L.S., Serpokrylova I.Ju., Sil’nikov V.N., Lavrik O.I. Evaluation method of activity of nucleotide excision repair system in mammals. Patent RF N.2492242, 2013.
2. Fedorova A.A., Goncharova E.P., Koroleva L.S., Sil’nikov V.N., Vlassov V.V., Zenkova M.A. Agent for inactivating DNA viruses. Patent RF N.2480478, 2013.
3. Fedorova A.A., Goncharova E.P., Burakova E.A., Sil’nikov V.N., Vlassov V.V., Zenkova M.A. Agent showing antiviral activity on DNA-viruses. Patent RF N.2487876, 2013.

RFBR (Grants of the Russian Foundation for Basic Research)

• N.14-04-01018 “Novel tools for inhibition of DNA repair enzymes on the basis of phosphorylated nucleoside derivatives” (2014-2016)
• N.14-04-00274 “Development of methods for producing nanosize nucleoside delivery system into mammalian cells in order to create effective antiviral drugs” (2014-2016)

Interdisciplinary Integration Project of the Presidium of SB RAS (2012-2014)

• N.60 “Multinuclear magnetic resonance spectroscopy and tomography – the basis of the integrated approach for the development of nucleic acid-based antitumor drugs”

Laboratory has the equipment for work on synthesis and proof of a structure of complicated organic molecules and the modified biopolymers.
Besides the standard equipment, laboratory also has solid-phase peptide synthesizer of original design, allowing to carry out solid-phase organic synthesis;

• synthesizer of oligonucleotides;
• analytical chromatographs (Milichrom) of various modifications.