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Interaction de l'or avec des peptides modèles de doigts de zinc : caractérisation de la complexation des sels d'or et application à la toxicologie des nanoparticules d'or

Abstract : Gold(I) complexes such as auranofine and aurothiomalate have been used as therapeutic agents for the treatment of rheumatoid arthritis for several decades. More recently, several gold(I) and gold(III) complexes have shown important in vitro anticancer properties. However, because of the high affinity of gold for sulfur and selenium ligands, these complexes interact with lots of proteins in a non-specific manner. This explains some of the side effects observed in patients treated with gold complexes and also why the mechanism of action of these complexes remains misunderstood. Among all the therapeutic target of gold salts that has been proposed, zinc fingers proteins are very interesting targets. Indeed, these proteins are very abundant (ca. 8 % of human proteome) and are involved in key processes of the cell (genes regulation, transcription, apoptose, DNA repair, resistance to oxidant stress…). These proteins contains a Zn(Cys)4-x(His)x (x = 0-2) center where zinc assure the proper fold and function of the protein. We were interested to study the interaction of some gold(I) and gold(III) complexes with zinc finger proteins by using peptidic models these zinc sites. By using different spectroscopic methods, we have characterized the products obtained by reaction between the zinc fingers and the gold salts and determined the kinetics of zinc displacement by gold.
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Aurélie Jacques. Interaction de l'or avec des peptides modèles de doigts de zinc : caractérisation de la complexation des sels d'or et application à la toxicologie des nanoparticules d'or. Chimie inorganique. Université de Grenoble, 2013. Français. ⟨NNT : 2013GRENV075⟩. ⟨tel-01555528⟩

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