Preorganized Peptide Scaffolds as Mimics of Phosphorylated Proteins Binding Sites with a High Affinity for Uranyl

Matthieu Starck†‡, Nathalie Sisommay†‡, Fanny A. Laporte†‡, Stéphane Oros†‡, Colette Lebrun†‡, andPascale Delangle*†‡

† Université Grenoble Alpes, INAC-SCIB, F-38000 Grenoble, France

‡ CEA, INAC-SCIB, F-38000 Grenoble, France

Inorg. Chem., Article ASAP

DOI: 10.1021/acs.inorgchem.5b02249

Publication Date (Web): November 19, 2015

Copyright © 2015 American Chemical Society

*E-mail: pascale.delangle@cea.fr.

Synopsis

Cyclic peptides with a β-sheet structure bearing two phosphoserines and two glutamic acids were developed to mimic high-affinity binding sites for uranyl found in proteins such as osteopontin, which is believed to be a privileged target of this ion in vivo. They were revealed to efficiently chelate uranyl (KC ≈ 1010, at pH 7.4) with a large contribution from the phosphorylated residues as in the protein.

http://pubs.acs.org/doi/10.1021/acs.inorgchem.5b02249

Abstract

Cyclic peptides with two phosphoserines and two glutamic acids were developed to mimic high-affinity binding sites for uranyl found in proteins such as osteopontin, which is believed to be a privileged target of this ion in vivo. These peptides adopt a β-sheet structure that allows the coordination of the latter amino acid side chains in the equatorial plane of the dioxo uranyl cation. Complementary spectroscopic and analytical methods revealed that these cyclic peptides are efficient uranyl chelating peptides with a large contribution from the phosphorylated residues. The conditional affinity constants were measured by following fluorescence tryptophan quenching and are larger than 1010 at physiological pH. These compounds are therefore promising models for understanding uranyl chelation by proteins, which is relevant to this actinide ion toxicity.