Laboratory of Medical Biotechnology

CONTACTS

+7-(499)-246-33-80

Nicolai N. Sokolov D.Sc., professor

Abdulla Hilial

Elena V. Mihalchenko

RESEARCH

Obtaining genetically engineered mutant homologs of L- asparaginase RrA from Rh. Rubrum and thermophilic L- asparaginases, characterization of their catalytic, physicochemical and structural properties, optimization of growing conditions of producer strains. Optimization of obtaining, isolation and purification of the most promising mutant variants of L- asparaginases.

Investigation of the antitumor properties of genetically engineered thermophilic L- asparaginases and mutant homologs of L- asparaginase RrA on various cell lines in vitro and in vivo experiments.

Development of modified PEG and (or) chitosan preparations of recombinant L- asparaginase RrA from Rh . Rubrum with improved biopharmaceutical properties and less immunogenicity for use in oncotherapy. Investigation of the effect of RrA conjugates with PEG- chitosan on the catalytic and physicochemical properties of the enzyme and its mutant forms.

The role of EndoG endonuclease in the regulation of alternative splicing.

The effect of low molecular weight compounds on the activity of telomerase in tumor cells.

Splice switching oligonucleotides for the regulation of apoptotic processes.

ONGOING PROJECTS

  • New L- asparaginase extremophilic microorganisms (grant RFBR 19 -08- 01112A)

COMPLETED PROJECTS

  • Search for a molecular target and assessment of the pharmacological potential of biosynthetic precursors and metabolites of brassinosteroids in prostate carcinoma cells as promising new antitumor drugs (Grant RFBR, no. 15-04-99711)
  • "Polypeptide cassette" to balance the rations of key amino acids in poultry (Grant RSF no. 16-16- 04086 2016 - 2018)
  • “A study of the relationship between the structure and functions of L- asparaginase from Rhodospirillum rubrum by site-directed mutagenesis” (RFBR project No. 15-34-70020 mol_a_mos 2016-2017)
  • Regulation of the catalytic properties of the recombinant Erwinia carotovora l- asparaginase using PEG- chitosan co-polymers (RFBR grant, no. 14-04-00325).
  • Development of an experimental-production technology for obtaining a substance, creating samples of a dosage form, preclinical testing of a substance, structural and functional study and obtaining modified forms with improved pharmacological properties of the recombinant Erwinia carotovora L- asparaginase (ISTC grant no. 2828).
  • Creation of a producer strain of recombinant L- asparaginase Erwinia carotovora and development of a large-scale method for purification of an enzyme with high antitumor activity (ISTC Grant no. 1263).
  • The molecular basis for the drug resistance of human leukemia cells to bacterial L- asparaginase (RFBR grant, no. 06-04-49792).
  • New bacterial L- asparaginases: the study of the structural and functional diversity of enzymes and the production of analogues with improved pharmacological properties ”(Grant RFBR, No. 04-04- 49085a .).
  • Epitope mapping of L- asparaginase and obtaining recombinant hypoallergenic forms of the enzyme. (Grant of the RFBR, no. 02-04- 49002a ).
  • Search and analysis of mimotopes and insulin peptidomimetics. (RFBR grant, no. 99-04-48544).
  • Development of approaches to loco-regional therapy of human malignant tumors by activating antitumor drugs with genetic constructs expressing cytochromes of the P450 family (Grant of the Ministry of Science in the framework of Project 05 “ Genodiagnosis and gene therapy of socially significant human diseases”.).
  • The creation of biocatalytic and analytical devices based on semi-artificial and recombinant cytochromes for monitoring drugs and studying the synthesis of steroids. (Grant INCO-Copernicus no. ERB3512PL965070 (Contract no. ERBIC15CT960810)).
  • Creating a producer strain of recombinant L- asparaginase Erwinia carotovora. (Grant of the Ministry of Science in the framework of the Program "The latest methods of bioengineering").
  • A method of producing a recombinant polypeptide TnaCheY-mut, recombinant polypeptide TnaCheY-mut, recombinant plasmid pGD TnaCheY-mut gene encoding TnaCheY-mut, strain Escherichia coli - produtsent recombinant polypeptide TnaCheY - mut, 2018 2018143308, Grishin D.V., Sokolov N.N., Pokrovsky M.V., Alexandrov S.S., Pokrovsky V.S.
  • The method of obtaining the recombinant elastomeric domain Trib-2 mut, the genetic engineering construct pGD Trib 2 mut, which determines the biosynthesis of Trib-2 mut in E cells. coli, strain-producing E. coli M15/pGD Trib 2 mut and a method for producing a polymer material based on this protein, 2015, 2015139343, Grishin D.V., Sokolov N.N., Abakumova O.Yu., Podobed O.V., Pokrovskaya M.V., Alexandrov S.S.
  • A method of producing a substance stimulating regeneration of damaged liver, 2014, 2,548,750, Halperin E.I., Dyuzheva T.G., Abakumova O.Yu., Platonova L.V.
  • The recombinant plasmid DNA pACYC_LANS (KM, the strain Escherichia coli BL21 (DE3, transformed with a recombinant DNA pACYC_LANS (KM, and a method for producing recombinant L-asparaginase Erwinia carotovora, 2010, 2,441,916, Sidoruk K.V., Bogusz V.G., Eldar M.A., Goncharova O.V., Chugunova N.M., Pokrovsky M.V., Alexandrov S.S., Omelyanyuk N.M., Sokolov N.N.
  • A method of obtaining a substance of recombinant L-asparaginase Erwinia carotovora, 2010, Karasev V.S., Bochkova O.P., Chugunov A.M., Melik-Nubarov N.S., Grozdova I.D., Chernovskaya T.V., Denisov L.A., Rudenko E.G., Morozova E.L., Bogush V.G., Sidoruk K.V., Koltun I.O., Skatova G.E., Abakumova O.Yu., Podobed O.V., Sokolov N.N.
  • A method for detecting strains of bacteria producing L-asparaginase, 2008, 2398876, Pokrovsky M.V., Sokolov N.N., Pokrovsky V.S., Archakov A.I., Gusev D.A.
  • Means of exhibiting anti-tumor activity, in 2008, 2,376,020, Tochilkin A.I., Belyaeva N.F., Abakumov O.Yu., Podobed O.V.
  • PCT - patent, 2003, WO03018742, Sokolov N.N. et al.
  • The recombinant plasmid DNA pACYCLANS for transfer and expression in cells of Escherichia coli gene L-asparaginase Ervinia Carotovora (ECAR-LANS) and method for its preparation by recombinant ECAR-LANS of biomass of strain E.coli-producer, 2002, 2,224,797, Eldar M.A., Zhgun A.A., Gervaziev Yu.In., Aleksandrova S.S., Bogusz V.R., Sidoruk K.V., Sveshnikov E.V., Borisov A.A., Omel'yanyuk N.M., Archakov A.I., Scriabin K.R., Sokolov N.N.
  • Gene L-asparaginase Ervinia Carotovora and strain Escherichia coli VKPM №In-8174 - producing L-asparaginase Ervinia Carotovora, 2001, 2,221,868, Eldar M.A., Zhgun A.A. , Gervaziev Yu.V., Aleksandrova S.S., Omel'yanyuk N.M ., Archakov A.I., Scriabin K.R ., Sokolov N.N
  • A method for the photodynamic treatment of acute and chronic purulent sinusitis, 2002 , 2228775, Nasedkin A.N., Reshetnikov A.V., Grachev S.V., Zalevsky I.L., Zenger V.G., Kemov Yu.V., Selin V.N., Abakumov O.Yu. and others
  • The photosensitizer and a method for its preparation, 2001, 1,283,956, Resetnicov A.V., Zalewski I.L., Kemov Y.V., Ivanov A., Karmenyan A.A., Gradyushko A.T., Laptev V.P., Neugodova N.P., Abakumov O.Yu. and etc.
  • A method for producing restriction endonuclease BspDI, 1990, 1,707,077, Sokolov N.N., Anikeycheva N.V., Fmtsner A.B., Samko O.T. Kalugin A.A., Horoshutina E.B., Librik G.I.
  • Bacterial strain of Bacillus brevis - producing restriction BBV of Bi, 1990 1,832,129, Sokolov N.N., Anikeycheva N.V., Eldar M.A., Fintser A.B., Karpychev I.V., Kalugin A.A., Samko O.T., Horoshutina E.B., Librik G.I.
  • Bacterial strain of Bacillus alvei - producing restriction Bav BII, 1990 1,761,803, Sokolov N.N., Fodor I.I., Fintser A.B.
  • The strain of the bacterium Bacillus coagulans - producer of restriction enzyme Bco AI, 1990, 1761804, Sokolov N.N., Anikeicheva N.V., Eldarov M.A., Fintzer A.B., Karpychev I.V., Kalugin A.A., Samko O.T., Horoshutina E.B., Librik G.I.
  • Bacterial strain of Bacillus alvei - producing restriction Bav AI, 1990, 1,678,833, Sokolov N.N, Fodor I.I.
  • A method for producing restriction endonuclease BbvAI, 1990, 1,712,415, Sokolov N.N., Fitsner A.B., Anikeycheva N.V., Horoshutina E.B., Samko O.T., Kalugin A.A.
  • The strain of bacteria of Achromobacter an agile - producing restriction Aag525I, 1989, 1,648,976 Sokolov N.N.
  • Bacterial strain of Lactobacillus plantarum - producing restriction LPlI, 1989, 1,678,832, Sokolov N.N., Fodor I.I,. Fintser A.B.,. Anikeycheva N.V., Kalugin A.A., Horoshutina E.B., Samko O.T., Kovalenko N.A., Eldar M.A.
  • The nutrient medium for culturing bacteria of the strain Pseudomonas airuginosa GISCO 134-producing restriction enzyme Rye II-, 1988, 1,561,506, Boykov Y.N., Viestur Z.A., Sokolov N.N., Fintser A.B., Anikeycheva N.V.
  • A process for preparing the solid phase support with a trityl groups, 1988, 1,651,262, Cherkasov T.A., Vonsky V.G ., Leikin Y.A., Kovalenko N.A., Sokolov N.N.
  • A method for producing restriction endonucleases PaeI, 1988, 1,592,333, Sokolov N.N., Fitsner A.B., Boykov Y.N., Horoshutina E.B., Kalugin A.A.
  • A method of producing a substance, which stimulates the proliferative process card endocrine pancreas, 1986, 1,412,061, Halperin E.I., Abakumova O.Yu., Ionochkina N.N.
  • A strain of Pseudomonas Aeruginosa-18 - producer endonuclease restriction Rae 11, 1985, 1,314,669, Sokolov N.N., Fodor I.I, Fintser A.B., Horoshutina E.B., Anikeycheva N.V., Samko O.T., Kolosha V.O.
  • A method for producing restriction endonuclease recognizes and cleaves the nucleotide sequence 5'ACATC↓C, 1249935, 1984, Sokolov N.N., Fodor I.I., Fitsner A.B., Horoshutina È.B,, Anikeycheva N.V., Kolosha V.O., Vautrin I.I.
  • A method for determining the activity of restriction endonucleases, 1983, 1,170,777, Heyslere M.Ya., Zilbere A.M., Sokolov N.N., Votrin I.I., Fintser A.B., Filipchenkova L.P., Shiverskih M.M.
  • A method for producing an enzyme preparation with a restriction enzyme activity, 1983, 1,160,743, Heyslere M.Ya., Shiverskih M.W., Ansberg S.E., Yasukevich A.K., Sproģe V.A., Fitsner A.B., Sokolov N.N., Votrin I.I.
  • A method for producing restriction enzymes, 1983, 1,163,637, Heyslere M.Ya., Shiverskih M.W., Ansberg S.E., Fitsner A.B., Sokolov N.N., Votrin I.I.
  • A method of producing a restriction enzyme Bam HI, 1982, 1,078,930, Heyslere M.YA., Filipchenkova LP, Šmite I.A., Ansberg S.E., Fintser A.B., Sokolov N.N., Votrin I.I.
  • The nutrient medium for the cultivation of Bacillus amyloliquefaciens - producer of BamH I restrictase, 1982, 1095642, Šmite I.A., Viesture Z.A., Heyslere M.Ya., Ansberg S.E., Aren A.K, Votrin I.I., Sokolov N.N.
  • Center for Biotechnology RAS, group of genetic engineering of mushrooms, laboratory of biomedical research
  • Federal State Institution Scientific Research Center of Russia (Serpukhov, Moscow Region)
  • Biotechnological company "CJSC Biocad" (Petrovo-Dalnee, Moscow Region)
  • Russian Center for oncology research
  • "BioChemMak" ST LLC
  • SSC RF Federal State Unitary Enterprise "GosNIIgenetika"
  • Plyasova A.A., Mendeleev Russian state technical University "Investigation of interaction of bacterial L-asparaginases with tumor cells"
  • Alayeva E.A., Lomonosov MIREA - Russian Technological University "Isolation of recombinant l-asparaginase Erwinia carotovora and preparation of the liposomal form of the enzyme»
  • Borisova A.A., Mendeleev Russian medical University, "Creation of a genetic design of the cytochrome P450 2B6 gene for use in combined chemo / gene therapy of tumors"
  • Kolomeychuk N., Lomonosov MIREA - Russian Technological University, "Synthesis of cationic lipids for delivery of genetic material"
  • Kuchumova A.V., Scriabin Moscow veterinary academy, "Epitope mapping of recombinant l-asparaginase Erwinia carotovora by phage display method"
  • Abramova O.S. "Immunochemical study of destructive processes in the nervous tissue in various pathologies of the nervous system". Biol. Sciences.
  • Borisova A.A. "Recombinant L-asparaginase of Erwinia carotovora: optimization of expression, isolation and properties". Biol. Sciences.
  • Gervaziev Yu.V. "Construction of the eespression system of the inducible isoform of nitric oxide synthase in Escherichia coli cells". Biol. Sciences.
  • Gladilina Yu.A. "Cloning, expression and characterization Of l-asparaginase of Helicobacter pylori with antitumor activity". Biol. Sciences
  • Kolomeychuk S.N. "Development of an approach to tumor gene therapy using the human cytochrome CYP450 2B6 gene". Biol. Sciences.
  • Korolev S.V. "Screening, isolation and study of specificity of new restriction endonucleases". Biol. Sciences
  • Kuchumova A.V. "Pegylation of recombinant L-asparaginase ERWINIA CAROTOVORA in order to enhance its therapeutically significant properties". Biol. Sciences.
  • Solodar L.I. "Comparative characteristics of variants of expression systems in E. coli cells of modified forms of rabbit and 1A2 human cytochromes P450". Biol. Sciences.