Laboratory of Medical Biotechnology

Dmitry D. Zhdanov Head of Lab
D.Sc.

CONTACTS

+7 (499)-246-33-80

Nicolai N. Sokolov D.Sc., professor

Yulia A. Gladilina Ph.D.

Anastasia N. Shishparenok



Varvara G. Blinova

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

  • Structural and functional characteristics of pseudoviral particles of the polio virus after inactivation by a chemical method and accelerated electrons. (RSF Grant 23-15-00471)
  • Modulation of suppressor activity of human regulatory T cells by inducing alternative splicing of FoxP3 pre-mRNA (RSF Grant 23-24-00326)
  • Development and characterization of mutant and conjugated forms of L-asparaginase from the extremophilic archaeon Thermococcus sibiricus for use in biomedicine and the food industry. Together with the Federal Research Center of Biotechnology of the Russian Academy of Sciences (RSF Grant 22-74-10100)

COMPLETED PROJECTS

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

avatar none  Blinova V.G., Gladilina Y.A., Abramova A.A., Eliseeva D.D., Vtorushina V.V., Shishparenok A.N., Zhdanov D.D. (2024) Modulation of Suppressive Activity and Proliferation of Human Regulatory T Cells by Splice-Switching Oligonucleotides Targeting FoxP3 Pre-mRNA, Cells, 13(1), 77. DOI:10.3390/cells13010077

avatar none  Latysheva A.S., Zolottsev V.A., Veselovsky A.V., Scherbakov K.A., Morozevich G.E., Zhdanov D.D., Novikov R.A., Misharin A.Y. (2023) Oxazolinyl derivatives of androst-16-ene as inhibitors of CYP17A1 activity and prostate carcinoma cells proliferation: Effects of substituents in oxazolinyl moiety, Journal of Steroid Biochemistry and Molecular Biology, 230, 106280. DOI:10.1016/j.jsbmb.2023.106280

avatar none  Dobryakova N.V., Zhdanov D.D., Sokolov N.N., Aleksandrova S.S., Pokrovskaya M.V., Kudryashova E.V. (2023) Rhodospirillum rubrum L-Asparaginase Conjugates with Polyamines of Improved Biocatalytic Properties as a New Promising Drug for the Treatment of Leukemia, Applied Sciences (Switzerland), 13(5), 3373. DOI:10.3390/app13053373

avatar none  Shishparenok A.N., Furman V.V., Zhdanov D.D. (2023) DNA-Based Nanomaterials as Drug Delivery Platforms for Increasing the Effect of Drugs in Tumors, Cancers, 15(7), 2151. DOI:10.3390/cancers15072151

avatar none  Dobryakova N., Zhdanov D., Dumina M., Aleksandrova S., Pokrovskaya M., Genin A., Shishparenok A., Zhgun A., Kudryashova E.V. (2023) Thermal Inactivation Mechanism and Structural Features Providing Enhanced Thermal Stability of Hyperthermophilic Thermococcus sibiricus L-Asparaginase in Comparison with Mesophilic and Thermophilic L-Asparaginases, Catalysts, 13(5), 832. DOI:10.3390/catal13050832

avatar none  Blinova V.G., Vasilyev V.I., Rodionova E.B., Zhdanov D.D. (2023) The Role of Regulatory T Cells in the Onset and Progression of Primary Sjögren’s Syndrome, Cells, 12(10), 1359. DOI:10.3390/cells12101359

avatar none  Dumina M., Zhdanov D., Zhgun A., Pokrovskaya M., Aleksandrova S., Veselovsky A., El’darov M. (2023) Enhancing the Catalytic Activity of Thermo-Asparaginase from Thermococcus sibiricus by a Double Mesophilic-like Mutation in the Substrate-Binding Region, International Journal of Molecular Sciences, 24(11), 9632. DOI:10.3390/ijms24119632

avatar none  Shishparenok A.N., Gladilina Y.A., Zhdanov D.D. (2023) Engineering and Expression Strategies for Optimization of L-Asparaginase Development and Production, International Journal of Molecular Sciences, 24(20), 15220. DOI:10.3390/ijms242015220

avatar none  Dobryakova N.V., Zhdanov D.D., Sokolov N.N., Aleksandrova S.S., Pokrovskaya M.V., Kudryashova E.V. (2022) Improvement of Biocatalytic Properties and Cytotoxic Activity of L-Asparaginase from Rhodospirillum rubrum by Conjugation with Chitosan-Based Cationic Polyelectrolytes, Pharmaceuticals, 15(4), 406. DOI:10.3390/ph15040406

avatar none  Shumyantseva V., Bulko T., Pronina V., Kanashenko S., Pokrovskaya M., Aleksandrova S., Zhdanov D. (2022) Electroenzymatic model system for the determination of catalytic activity of Erwinia carotovora L-asparaginase, Processes, 10(7), 1313. DOI:10.3390/pr10071313

avatar none  Agafonova L., Zhdanov D., Gladilina Yu., Kanashenko S., Shumyantseva V. (2022) A pilot study on an electrochemical approach for assessing transient DNA transfection in eukaryotic cells, Journal of Electroanalytical Chemistry, 920, 116635. DOI:10.1016/j.jelechem.2022.116635

avatar none  Tawfik H.O., El-Hamaky A.A., El-Bastawissy E.A., Shcherbakov K.A., Veselovsky A.V., Gladilina Y.A., Zhdanov D.D., El-Hamamsy M.H. (2022) New Genetic Bomb Trigger: Design, Synthesis, Molecular Dynamics Simulation, and Biological Evaluation of Novel BIBR1532-Related Analogs Targeting Telomerase against Non-Small Cell Lung Cancer, Pharmaceuticals, 15(4), 481. DOI:10.3390/ph15040481

avatar none  Pokrovskaya M.V., Pokrovsky V.S., Aleksandrova S.S., Sokolov N.N., Zhdanov D.D. (2022) Molecular Analysis of L-Asparaginases for Clarification of the Mechanism of Action and Optimization of Pharmacological Functions, Pharmaceutics, 14(3), 559. DOI:10.3390/pharmaceutics14030599

avatar none  Neborak E.V., Kaldybayeva A.B., Bey L., Malmakova A.Y., Tveritinova A.S., Hilal A., Yu V.K., Ploskonos M.V., Komarova M.V., Agostinelli E., Zhdanov D.D. (2022) Anticancer Cytotoxic Activity of Bispidine Derivatives Associated with the Increasing Catabolism of Polyamines, Molecules, 27(12), 3872. DOI:10.3390/molecules27123872

  • Modified TsA gene encoding thermostable L-asparaginase from the archaea Thermococcus sibiricus, recombinant strain of Escherichia coli - producer of thermostable L-asparaginase and a method for purifying this enzyme, 2022, 2022106430/10(013385) Dumina M.V., Zhgun A.A. , Aleksandrova S.S., Pokrovskaya M.V., Sokolov N.N. Zhdanov D.D.
  • 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"
  • Koroleva S.A., Federal State Budgetary Educational Institution of Higher Education "Moscow Polytechnic University", bachelor's final qualifying work "Enzymatic and cytotoxic activities of L-asparaginase immobilized on a bacterial cellulose matrix."
  • Makarova D.A., Federal State Budgetary Educational Institution of Higher Education "Moscow Polytechnic University", bachelor's final qualification work "Study of the cytotoxic activity of L-asparaginases of extremophilic microorganisms"
  • Plyasova A.A., Federal State Budgetary Educational Institution of Higher Education “Russian Chemical-Technological University named after D.I. Mendeleev", master's final qualifying work "Inhibition of telomerase by L-asparaginase from Rhodospirillum rubrum during penetration into cancer cells through the clathrin-dependent pathway of endocytosis."
  • Kutukov R.R., Federal State Budgetary Educational Institution of Higher Education "Moscow Polytechnic University", bachelor's final qualifying work "Polyamines as chemotherapeutic cytoprotectors"
  • 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.