Laboratory of molecular design and synthesis
- Obtaining the compounds with antiviral activity.
- Creating the fluorescent DNA probes.
- Developing oligonucleotide conjugates as blocks for DNA nanostructures.
- Creating the mass-spectrometric labels for the detection of biomolecules.
- Development of innovative methods of synthetic organic chemistry and innovative schemes of synthesis of organic compounds
- A practical preparation of compounds of different classes, such as benzoheterocycles, arylsulfamides and arylsulfonic acids, polycyclic and cage compounds, arylboronic acids, drug degradation products, antigens and haptens, fluorescent labels, unconventional amino acids, spin-labeled amino acids of the chromophore and photosensitizing compounds, low-molecular weight compounds.
- The formation of interchain excimer pyrene in the major groove of DNA (ChemBioChem, 2003, 4:841).
- 1-Phenylethynylpyrene was proposed as improved excimer forming fluorescent label for nucleic acids (Nucleosides Nucleotides, 1997, 16:1461; Eur. J. Org. Chem., 2004, 1298; Bioconjugate Chem., 2007, 18:1972) and used in various types of DNA probes (Mutation Res., 2006, 599:144; Meth. Mol. Biol., 2009, 578:209; Chem. Eur. J., 2008, 14:11010; Chem. Commun., 2010, 46:8362; Bioconjugate Chem., 2011, 22:533; Analyst, 2016, 141:1331).
- For the first time, fluorescent dyes were attached to a nucleobase through ethynyl linker (Биоорган. химия, 1996, 22:923; ChemBioChem, 2006, 7:810). A new class of antiviral compounds was found among these nucleosides. The compounds are active against herpes simplex virus type 1, hepatitis C virus and several other enveloped viruses (Биоорган. химия, 2003, 29:289; Вопросы вирусологии, 2006:34; Tetrahedron, 2006, 62:1279; Org. Biomol. Chem., 2006, 4:1091; PNAS USA, 2010, 107:17339; J. Virol., 2013, 87:3640; Med. Chem. Commun., 2016, 7:495).
- New mass-spectrometric labels were developed (Org. Biomol. Chem., 2008, 6:4593; Масс-спектрометрия, 2015, 12:253; Analyst, 2016, 141:3289) and the method of single nucleotide polymorphism detection using MALDI spectrometry was proposed (Anal. Chem., 2008, 80:2342; Meth. Mol. Biol., 2009, 578:345) and the analysis method of aminoglycoside antibiotics (Acta Naturae, 2016, 8:128).
- The application of azide-alkyne cycloaddition was revealed for the synthesis of DNA conjugates (Биоорган. химия, 2010, 36:437) including building blocks for the DNA nanostructures self-assembly (Изв. АН, Сер. хим., 2006:1220; Tetrahedron, 2008, 64:1467; Chem. Commun., 2013, 49:511; Org. Lett., 2014, 16:4590; Tetrahedron, 2016, 72:2386) and for the preparation of efficient fluorogenic DNA probes for real-time PCR assay (Anal. Bioanal. Chem., 2012, 404:59; Analyst, 2014, 139:2867; Analyst, 2016, 141:1331; Anal. Meth., 2016, 8:5826; Mol. Cell. Probes, 2016, 30:285).
- Oligopeptide components of Plm II protease inhibitors – ω-hydroxy-L-α-amino acids – were synthesized.
- A new preparative method for the synthesis argiope, synthesized 100 g of this natural toxin. Founded method was used in the synthesis of argiope analogues.
- Efficient methods for synthesis were designed and representative set of substituted 2-thiazolyl-1-alkyl(aryl)ethanol, prospective templates for new pharmacological agents.
- Synthetic schemes were developed and synthesis of haptens were conducted, which play an important role in an enzyme immunoassay toxic components of household detergents that pollute the environment, modern pesticides and antibiotics.
- The methods of synthesis were designed and photoswitchable protein fragment to create a controlled secondary structure elements was received; photoactivated labels for studies of receptor systems; fluorescent labels for the study of structure and functions of nucleic acids; photosensitizing agents; fluorescent indicators.
- As a part of the Program of the Presidium of the RAS "Biosphere Origin and Evolution" were analyzed the abiogenous variations of the adenine formation conditions and condensation of adenine with ribose and ribosophosphate using the methods of computer synthesis; monosaccharides library were formed, methods of determining the methods of gas chromatography-mass spectrometry and GLC were developed.
- New subclass of modified nucleosides having high activity against enveloped viruses was founded. Peruse detected earlier (Bioorgan. Chemistry, 29 (3), 289-294 (2003), Nucleosides, Nucleotides & Nucleic Acids, 24 (5/7), 923-926 (2005), Tetrahedron, 62 (6), 1279 -1287 (2006) Problems of Virology, 2006 (1), 34-38, Org. Biomol. Chem., 4 (6), 1091-1096 (2006)) identified a class of antiviral compounds from the group of substances active against enveloped viruses. Specifically, IC50 5- (perylene-3-yl) ethynyl-2'-deoxyuridine was 50 nmol / L for herpes simplex virus type 1 and 180 nmol / L for hepatitis C. A characteristic feature of active nucleosides structure is the availability of an aromatic residue hydrocarbon perylene rigidly attached to the nucleobase via a triple bond. It is suggested that the unique structure of the resulting compounds is responsible for their incorporation into the virion membrane, resulting in the fusion of the virion to the cell (infection) becomes very disadvantageous process (Figure). The novel compounds practically cytotoxic.
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