Partenaires et organisations internationales
(Anglais)
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AT, BE, DK, FI, FR, DE, EL, HU, IE, IL, IT, MT, NL, NO, PL, PT, ES, SE, CH, UK
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Résumé des résultats (Abstract)
(Anglais)
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Platinum coordination complexes represent one of the most potent antitumor drugs. The focus of our research is the interaction of abundant intracellular thiol metallothionein (MT) with different Pt(II) drugs and a possible role of Pt(II)-MT complexes to act as a reservoir for DNA platination. It is well established that MT through Pt(II) detoxification plays an important role in drug resistance. Our ESI-MS studies showed that while cis-Pt(II) complexes upon their interaction with MT became inactivated through their tetrathiolate coordination, the recently developed antitumor trans-Pt(II) compounds retained both ammine ligands due to the trans-effect of sulfur. However, although the trans-Pt(II)-MT forms remained potentially active for DNA platination, no Pt(II) transfer to pSP73 plasmid or to a synthetic DNA oligomer could be observed. Independently, by Western blot analysis of the protein we could show for the first time that only certain cis- and trans-Pt(II) drugs in the presence of MT and pSP73 plasmid form stable ternary complexes, i.e., MT-Pt(II)-DNA. This finding may have important consequences for DNA repair.
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