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Invited researcher Michael Keith Bowman
Contract number
14.W03.31.0034
Time span of the project
2018-2020

As of 30.01.2020

52
Number of staff members
28
scientific publications
General information

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

Strategy for Scientific and Technological Development Priority Level: в


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

  • We have developed a strategy for modernizing electron paramagnetic resonance (EPR) pulse spectrometer    and signed contracts for purchase of hi-tech modern equipment for EPR spectroscopy and a tomography. The equipment will be used for solving current fundamental and applied problems in research of structure and functions of proteins and nucleic acids, pathological processes in various diseases.
  • Our team has developed convenient methods for synthesis of spatially hindered radicals of the pyrrolidine series. At the moment these nitroxyl radicals are the most stable against reduction in the world. On the basis of these radicals we have produced a number of spin labels and probes with pH-dependent EPR spectrum that can be used in in vivo biophysical research or in structural biology for investigating mechanisms of functioning of biomolecules inside living cells. We have demonstrated efficiency of usage of such probes for non-invasive monitoring of changes of pH in tissues of live mice – carriers of xenographic tumors of various types.
  • We have produced a number of useful compounds including: a variety of nitroxyl radicals with fluoroformic spiropyran fragments; a variety of spin labels for research in the field of structural biology, a variety of bioradicals for structural research using dynamic polarization of nuclei.
  • Using the EPR method we have investigated magnetic resonance parameters (g-factor, supercurrent interaction constants, electron spin relaxation) of synthesized trityl and nitroxyl radicals. Produced spin labels can be used for studying structures of biomolecules and their complexes.

Implemented results of research: A number of synthesized chemical compounds (including: рН-sensitive spin probes with increased resistivity against reduction, nitroxyl radicals with fluorophilic spiropyran fragments, spin labels for research in the area of structural biology, bioradicals for structural research using dynamic polarization of nuclei) are promising spin probes and labels for wide usage in biophysical research, separate compounds or their modifications can be used in diagnostics and developing strategies of treatment of cardiovascular diseases, Alzheimer's disease, oncological diseases and others.

Education and career development:

  • We have developed a lecture course in modern methods of electron paramagnetic resonance (EPR) and their applications in biophysics, including results of the projects, the course was designed masters students and postgraduates of the Novosibirsk State University, Voevodsky Institute of Chemical Kinetics and Combustion of the Siberian Department of the Russian Academy of Sciences, International Tomography Center of the Siberian Department of the Russian Academy of Sciences and Nikolaev Institute of Inorganic Chemistry of the Siberian Department of the Russian Academy of Sciences. As a part of the course in 2019 employees of the Laboratory will read lectures and conduct seminars, case studies.
  • 2 candidate dissertations and one bachelor dissertation have been defended.

Organizational and structural changes: In 2019 after the delivery of the purchased equipment we will modernize the pulse EPR spectrometer which will allow us to significantly reduce duration and increase efficiency of experiments for researching structure of biocomplexes.

Collaborations:

Institute of Inorganic and Physical Chemistry of TU Darmstadt (Germany), Division of Bioengineering and Bioinformatics of the Hokkaido University (Japan), Martin Luther University Halle-Wittenberg (Germany), Institute of Radical Chemistry of the University of Aix-Marseille (France), Department of Biochemistry of the West Virginia University Cancer Institute (USA), Novosibirsk State University (Russia): joint research

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Bothe S., Nowag J., Klimavičius V., Hoffmann M., Troitskaya T., Amosov E., Tormyshev V., Kirilyuk I., Taratayko A., Kuzhelev A., Parkhomenko D., Bagryanskaya E., Gutmann T. and Buntkowsky G.
Novel Biradicals for Direct Excitation Highfield Dynamic Nuclear Polarization. The Journal of Physical Chemistry C 122(21): 11422–11432 (2018).
Komarov D., Ichikawa Y., Yamamoto K., Stewart N., Matsumoto S., Yasui H., Kirilyuk I., Khramtsov V., Inanami O. and Hirata H.
In Vivo Extracellular pH Mapping of Tumors Using Electron Paramagnetic Resonance. Analytical Chemistry 90(23): 13938–13945 (2018).
Lampp L., Rogozhnikova O., Trukhin D., Tormyshev V., Bowman M., Devasahayam N., Krishna M., Mäder K. and Imming P.
A Radical Containing Injectable In-situ-oleogel and Emulgel for Prolonged In-vivo Oxygen Measurements with CW EPR. Free Radical Biology and Medicine 130: 120–127 (2019).
Kuzhelev A., Krumkacheva O., Ivanov M., Prikhod’ko S., Adonin N., Tormyshev V., Bowman M., Fedin M. and Bagryanskaya E.
Pulse EPR of Triarylmethyl Probes: A New Approach for the Investigation of Molecular Motions in Soft Matter. The Journal of Physical Chemistry B 122(36): 8624–8630 (2018).
Rudnitskaya E., Kozlova T., Burnyasheva A., Kolosova N. and Stefanova N.
Alterations of hippocampal neurogenesis during development of Alzheimer's disease-like pathology in OXYS rats. Experimental Gerontology 115: 32–45 (2019).
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