Recent advances in uranyl binding in proteins thanks to biomimetic peptides

Abstract

Uranium is an element belonging to the actinide series. It is ubiquitous in rock, soil, and water. Uranium is found in the ecosystem due to mining and milling industrial activities and processing to nuclear fuel, but also to the extensive use of phosphate fertilizers. Understanding uranium binding in vivo is critical, first to deepen our knowledge of molecular events leading to chemical toxicity, but also to provide new mechanistic information useful for the development of efficient decorporation treatments to be applied in case of intoxication. The most stable form in physiological conditions is the uranyl cation (UO₂²⁺), in which uranium oxidation state is +VI. This short review presents uranyl coordination properties and chelation, and what is currently known about uranium binding to proteins. Although several target proteins have been identified, the UO₂²⁺ binding sites have barely been identified. Biomimetic approaches using model peptides are good options to shed light on high affinity uranyl binding sites in proteins. A strategy based on constrained cyclodecapeptides allowed recently to propose a tetraphosphate binding site for uranyl that provides an affinity similar to the one measured with the phosphoprotein osteopontin.

Keywords: Biomimetic peptide; Decorporation; Metal binding; Proteins; Uranyl.