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CHEMBIORAD Working Groups

Biologically of relevant small radicals (WG4)

WG Leader: Prof. Sara Goldstein; e-mail: sarag@vms.huji.ac.il

This group deals with the chemistry and reactivity of small biologically relevant radicals. The knowledge that is available on the kinetic and spectroscopic properties of these small radical species has still to be combined with the biological conditions. An effort has to be made to create a common research field linking the chemical and biological data in order to contribute to the solution of biological questions on the small radical activities.

The groups involved in WG4 are:

  1. Sara Goldstein (WG leader) - Hebrew University of Jerusalem (Israel)
  2. Zilvinas Anusevicius - Institute of Biochemistry, Vilnius (Lithuania)
  3. Georg Bauer - Universität Freiburg (Germany)
  4. Narimantas Cenas - Institute of Biochemistry, Vilnius (Lithuania)
  5. Milan Ciz - Institute of Biophysics AS (Czech Republic)
  6. Chryssostomos Chatgilialoglu - ISOF-CNR, Bologna (Italy)
  7. Ileana Dragutan - Romanian Academy, Bucharest (Romania)
  8. Jerzy Gebicki - Technical University of Lodz (Poland)
  9. Georg Gescheidt - Graz University of Technology (Austria)
  10. Bernard Golding - University of Newcastle upon Tyne (UK)
  11. Jens Hartung - TU Kaiserslautern (Germany)
  12. Jozsef Kaiser - University of Pannonia (Hungary)
  13. Markus Knipp - Max-Planck-Institut, Mülheim (Germany)
  14. Esa-Matti Lilius - University of Turku (Finland)
  15. Gabor Merenyi - Royal Institute of Technology (Sweden)
  16. Barry Parson - University of Leeds (UK)
  17. Gabor Speier - University of Pannonia (Hungary)
  18. Peter Wardman - University of Oxford (UK)

The main subjects for collaborative research are:

  • Chemistry of biologically relevant radicals to improve the existing knowledge.
  • Reactions of small radicals with biomolecules, e.g., lipids, proteins, nucleic acids.
  • Use of heterogeneous systems, e.g., liposome vesicles, for model studies of small radicals.
Tasks will involve the radical-based mechanisms of biological functions and radical damage.

Radical functioning:
Intermediate species in the functioning of selected radical enzymes with spectroscopic detection of intermediate radicals and their kinetic competence. Biomimetic models of the reactivity of small radicals toward membranes. Competitive pathways involving small radicals and correlation with cell signalling activities.

Radical damaging:
Mechanistic and product studies of the interaction of small radicals with biomolecules, and correlation with the biological activity or damage. Inhibition of the damage by common antioxidants and search for more efficient ones.

Some details of the WG4 tasks are:

  • Study of selected enzymes, e.g., glutamate mutase. Detection of radical intermediates and their kinetic competence.
  • Biomimetic models for reactive nitrogen and oxygen species in homogeneous and heterogeneous systems.
  • Reaction of nitrite-derived species with thiols and salivary uric acid. Individuation of the main species to be assayed in cell signalling activities.
  • Production of different small radicals (•NO, CO3•-, HO•, R2S•+) and competitive pathways in the functioning of macrophages during infections.
  • Mechanisms of radical mediated nitrosation and nitration of biologically relevant molecules.
  • Mechanistic and product studies of the interaction of S-centred radicals (MeS• or HS/S•-) with biomolecules, e.g., unsaturated lipids, with the potential to act as isomerising species or competitively producing lipid oxidation and nitration.
  • Interaction of CO3•- with model proline derivatives and sulphur compounds.
  • Assays for cell damage/repair caused by HO•, Fenton-type reactions and peroxynitrite.
  • Inhibition of the damage given by common antioxidants, and search for more efficient ones.

Collaboration with other WGs:

There will be activities in collaboration with other WGs in particular for the following subjects:
- Experiments in liposomes in collaboration with WG1.
- Interaction with WG2 for the study of protein damage.
- Iinteraction with WG3 for evaluation of the cell damage and repair pathways initiated by biologically relevant small radicals.
- Evaluation of apoptosis signalling in collaboration with all WGs and biological research units.