Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Scientific result | Nuclear Toxicology
Researchers from INAC have used a biomimetic approach to analyze the interactions of uranium with the biological molecules involved in the toxicity of this element. Phosphoproteins appear to be priority targets.
Uranium is an abundant natural element found in many ores and seawater. Despite its omnipresence, uranium does not play an essential role in living organisms. The molecular mechanisms responsible for its radiological and chemical toxicity are still poorly understood.
In vivo, the most stable uranium ion is uranyl cation UO22+ which preferentially interacts with four to six oxygen atoms in the plane perpendicular to the O=U=O bonds. Chemists from INAC have chosen short peptide sequences to mimic protein/metal interactions to determine their structural and thermodynamic characteristics. A cyclic peptide structure constraining electron-donating oxygen atoms in the equatorial plane of uranyl has been found to be particularly effective in producing a supramolecular edifice in which the peptide interacts with uranyl (uranyl complex).
By combining synthesis, chemical analysis, X-ray absorption spectroscopy and theoretical calculations, the researchers managed to correlate the amino acid sequence of the cyclic structure and the stability of the resulting uranyl complex. Phosphate groups (PO43-) were found to significantly enhance the affinity of biomimetic peptides with uranyl. Phosphoproteins such as osteopontin must therefore be considered as potential targets for uranyl in vivo.
Cyclic phosphopeptides to rationalize the role of phosphoamino acids in uranyl binding to biological targets, Chemistry-A-European Journal.
Preorganized Peptide Scaffolds as Mimics of Phosphorylated Proteins Binding Sites with a High Affinity for Uranyl, Inorganic Chemistry.Engineering Short Peptide Sequences for Uranyl Binding, Chemistry-A-European Journal.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.