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Contract number
14.W03.31.0034, 075-15-2021-614
Time span of the project
2018-2022

As of 01.11.2022

41
Number of staff members
79
scientific publications
2
Objects of intellectual property
General information

Name of the project: Multi-frequency electron paramagnetic resonance (EPR) for biochemical research


Goals and objectives

Research directions: Applications of modern methods of electron paramagnetic resonance (EPR) in current problems of biochemistry and biomedicine

Project objective: Enhancement and applications of state-of-the-art methods electron paramagnetic resonance (EPR) spectroscopy to modern problems of biochemistry and biomedicine that are crucially important for development of methods of diagnostics and designing strategies of treatment of socially important diseases such as cardiovascular diseases, Alzheimer's disease, oncological diseases and others.

The practical value of the study

Scientific results:

The main result is the creation of a new world-class laboratory on the grounds of the Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences (NIOC SB RAS), whose main academic direction is the development and application of advanced methods of electron paramagnetic resonance (EPR) spectroscopy in current problems of biochemistry and biomedicine. To achieve the goal of the project, we have solved problems of the creation and modernization of the experimental facilities, the development of new spin probes relying on nitroxyl and triarylmethyl radicals, the development of new pulse sequences in EPR spectroscopy, solving problems in the research of the structure of human ribosomal complexes and applying polymerization reactions to research tasks.

Main results of 2022:

  1. We have developed a modern Russian pulse EPR spectrometer in the Х- and Q-range with the capability of generating chirp microwave pulses of specified shape. In contrast to  the existing spectrometers, we are using the detection of the shape of spin echo and collecting information on the Fourier spectrum of spin echo.
  2. The Laboratory has developed a molecular design and a procedure for synthesizing  hydrophilic and hydrophobic spin tags and functional probes that are distinguished by high resistance to reduction. The synthesized radicals and biradicals are promising for applications in  biophysics and for creating new functional materials.
  3. We have demonstrated the use of nitroxide and trityl radical tags for measuring distance in situ with the use of a carrier of BtuB cobalamin. The use of these tags allowed to measure the distance for BtuB in E. coli and native external membranes.
  4. The synthesized spin probes have been used for the non-invasive research of extracellular acidification in animals, which indicates a metabolic shift in tumor cells and, along with tissue hypoxia, is a sign of a malignant tumor.

Implemented results of research: 

  • At the Laboratory we have created a modern Russian pulse EPR spectrometer in the Х- and Q-range with the capability of generating chirp-microwave pulses of specified shape. The device can compete with foreign EPR spectrometers in terms of its characteristics.
  • A number of synthesized chemical compounds (including рН-sensitive spin probes with increased resistance to reduction, spin tags for research in the domain of structural biology, biradicals for structural research with the use of dynamic nuclear polarization) are promising spin probes and tags for broad applications in biophysical research, individual compounds or their modifications can be used in diagnostics and developing treatment strategies for cardiovascular diseases, the Alzheimer’s disease, oncological diseases etc.
Education and career development:

  • 8 Candidate of Sciences dissertation, one Doctor of Sciences dissertation, 4 student theses have been prepared and defended.
  • We have developed and launched the education course «Modern methods of EPR spectroscopy and their applications in biophysics» for programs of specialist, master's degree, postgraduate school of NIOC SB RAS, Novosibirsk State University.
  • 6 textbooks and video lecture courses have been authored by employees of the Laboratory devoted to our area of study.

Organizational and structural changes: 

On the basis of NIOC SB RAS a world-class laboratory has been created in the research domain of development and application of advanced electron paramagnetic resonance (EPR)  spectroscopy methods  in current problems of biochemistry and biomedicine. 

Collaborations:

International Tomography Center of the Siberian Branch of the Russian Academy of Sciences (Russia), Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences (Russia), Institute of Chemical Kinetics and Combustion of the Siberian Branch of the Russian Academy of Sciences (Russia), Novosibirsk State University (Russia), University of Alabama (USA), Institute of Inorganic and Physical Chemistry of TU Darmstadt (Germany), Division of Bioengineering and Bioinformatics of Hokkaido University (Japan), Martin Luther University Halle–Wittenberg (Germany), Institute of Radical Chemistry of Aix–Marseille University (France), Department of Biochemistry of West Virginia University Cancer Institute (USA): joint research.

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l. lampp, o.yu. rogozhnikova, d.v. trukhin, v.m. tormyshev, m.k. bowman, n. devasahayam, m.c. krishna, karsten mäder, p. imming
A radical containing injectable in-situ-oleogelandemulgelforprolongedin-vivooxygen measurements with CW EPR, Free Radical Biology and Medicine, 2018, 10 (2019 Jan; 130:120-127)
o.a krumkacheva, i.o. timofeev, l.v politanskaya, y.f. polienko, e.v. tretyakov, o.yu. rogozhnikova, d.v. trukhin, v.m. tormyshev, a.s. chubarov, e.g. bagryanskaya, m.v. fedin
Triplet Fullerenes as Prospective Spin Labels for Nanoscale Distance Measurements by Pulsed Dipolar EPR Spectroscopy, Angewante Chemi Int Ed Engl, 2019, 09, (16, 58(38), 13271-13275)
o.a. krumkacheva, g.yu. shevelev, a.a. lomzov, n.s. dyrkheeva, a.a. kuzhelev, v. v. koval, v.m. tormyshev, y.f. polienko, m.v. fedin, d.v. pyshnyi, o.i. lavrik, e.g. bagryanskaya
DNA complexes with human apurinic/apyrimidinic endonuclease 1: structural insights revealed by pulsed dipolar EPR with orthogonal spin labeling Nucleic Acids Research, 2019, 09 (47, 15, 7767-7780)
a.a. malygin, o.a. krumkacheva, d.m. graifer, i.o. timofeev, a.s. ochkasova, m.i. meschaninova, a.g. venyaminova, m.v. fedin, m. bowman, g.g. karpova, e.g. bagryanskaya
Exploring the interactions of short RNAs with the human 40S ribosomal subunit near the mRNA entry site by EPR spectroscopy Nucleic Acids Research, 2019, 12 (47, 22, 11850–11860)
m. bretschneider, p.e. spindler, o.yu. rogozhnikova, d.v. trukhin, b. endeward, a.a. kuzhelev, e. bagryanskaya, v.m. tormyshev, t.f. prisner
Multi-Quantum Counting of Trityl Radicals Journal of Physical Chemistry Letters 2020, 07 (11,15)
s. ketter, a. gopinath, o. rogozhnikova, d. trukhin, v.m. tormyshev, e.g. bagryanskaya, b. joseph
In situ labeling and distance measurements of membrane proteins in E. coli using Finland and OX063 trityl labels Chemistry-A European Journal 2020, 11 (27)
a.g. matveeva, v.n. syryamina, v.m. nekrasov, m.k. bowman
Non-uniform sampling in pulse dipolar spectroscopy by EPR: the redistribution of noise and the optimization of data acquisition Physical Chemistry Chemical Physics 2021, 04 (23, 17)
k.n. bulygin, i.o. timofeev, a.a. malygin, d.m. graifer, m.i. meschaninova, a. g. venyaminova, o.a. krumkachev. m.v. fedin, l.yu. frolova, g.g. karpova, e.g. bagryanskaya
Two alternative conformations of mRNA in the human ribosome during elongation and termination of translation as revealed by EPR spectroscopy Computational and Structural Biotechnology Journal, 2021, 08 (19)
i.o. timofeev, l.v. politanskaya, e.v. tretyakov, yu.f. polienko, v.m. tormyshev, e.g. bagryanskaya, o.a. krumkacheva, m.v. fedin,
Fullerene-based triplet spin labels: methodology aspects for pulsed dipolar EPR spectroscopy Physical Chemistry Chemical Physics, 2022, 06, (24, 7, 4475-4484)
n.b. asanbaeva, l.yu. gurskaya, yu.f. polienko, t.v. rybalova, m.s. kazantsev, a.a. dmitriev, n.p. gritsan, n. haro-mares, t. gutmann, g. buntkowsky, e.v. tretyakov, e.g. bagryanskaya
Effects of Spiro-Cyclohexane Substitution of Nitroxyl Biradicals on Dynamic Nuclear Polarization, Molecules 2022, 05 (27, 10, 3252)
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