Actinide Complexation with Biomimetic Phosphorylated Molecules
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Actinide Complexation with Biomimetic Phosphorylated Molecules Samir Safi1,2, Marie Christine Charbonnel2, Gaelle Creff1,3, Aurélie Jeanson1, Sarah Mostapha2, Jerome Roques1, Eric Simoni1, Pier Solari4, Claude Vidaud3, Christophe Den Auwer2,5 1
Institut de Physique Nucléaire Orsay, Université Paris XI Orsay, 91405 Orsay, France
2
CEA Marcoule, Nuclear Energy Division, DRCP, 30207 Bagnols sur Cèze, France
3
CEA Marcoule, Life Science Division, iBEB/SBTN, 30207 Bagnols sur Cèze, France
4 5
Synchrotron SOLEIL, MARS beam line, 91192 Gif sur Yvette, France University of Nice Sophia Antipolis, Nice Chemistry Institute, 06108 Nice, France
ABSTRACT Most data available on the interaction of actinides with biological systems are based on physiological or biokinetic measurements, with scarce information on the structure of the actinide coordination site. This proceeding article describes an approach for structural elucidation of actinide biological complexes. Indeed most of c.a. actinide circulation pathways are unknown, as they accumulate mostly in bones, kidney and liver. In case of accidental release of radionuclide in the environment, internal contamination under either acute or chronic conditions has the potential to induce both radiological and chemical toxicity through significant interaction with the metabolome or proteome followed by possible functional modifications. For instance, the metalloproteins present primary, secondary and tertiary structures, and also different post-translational modifications, all playing a crucial role in interacting with their partners, which can be altered by actinide bonding. When tightly bound, metal ions are critical to the function, structure, and stability of the proteins, by disabling specific interactions through significant local or global conformational modifications. In order to overcome the intricacy of actinide chemistry combined with that of metalloproteins, a simplified study toward better understanding the interaction of actinides and biological systems using simple biomolecules such as amino acids has therefore been considered. Focus is made on the cation coordination site itself, given that conformational effects are not taken into account in this approach. In a first step, we have selected simple phosphorylated building blocks that may be considered as chemical representatives of some ubiquitous target metalloproteins or some important phosphorylated peptides or proteins. INTRODUCTION In case of accidental exposure to radioelements, internal actinide toxicity is related to both emitted radiation and to the in-vivo circulation scheme [1]. Blocking the biological pathways of the actinides in the human (or more generally mammalian) systems and/or increasing their elimination rate would considerably decrease the toxicity of these elements. While actual decorporating agents like DTPA (diethylenetriaminepentaacetic acid) are effective for plutonium (IV), clinical studies showed that extended treatment may cause liver failure [2]. Overall the need for a better understa
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