Engineering Short Peptide Sequences for Uranyl Binding

• Published in: Chemistry : a European journal 2014-12, Vol.20 (50), p.16566-16573
• Main Authors: Lebrun, Colette, Starck, Matthieu, Gathu, Vicky, Chenavier, Yves, Delangle, Pascale
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Binding; Binding Sites; Biocompatibility; bioinorganic chemistry; carboxylate ligands; Carboxylic Acids - chemistry; Cations; Chemistry; fluorescence; Oligopeptides - chemistry; Oligopeptides - metabolism; Peptides; Peptides, Cyclic - chemistry; Peptides, Cyclic - metabolism; Planes; Scaffolds; Stability; uranium; Uranium - metabolism
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201404546

Peptides are interesting tools to rationalize uranyl–protein interactions, which are relevant to uranium toxicity in vivo. Structured cyclic peptide scaffolds were chosen as promising candidates to coordinate uranyl thanks to four amino acid side chains pre‐oriented towards the dioxo cation equatorial plane. The binding of uranyl by a series of decapeptides has been investigated with complementary analytical and spectroscopic methods to determine the key parameters for the formation of stable uranyl–peptide complexes. The molar ellipticity of the uranyl complex at 195 nm is directly correlated to its stability, which demonstrates that the β‐sheet structure is optimal for high stability in the peptide series. Cyclodecapeptides with four glutamate residues exhibit the highest affinities for uranyl with log KC=8.0–8.4 and, therefore, appear as good starting points for the design of high‐affinity uranyl‐chelating peptides. Structured cyclic peptide scaffolds with four acidic residues are promising candidates to complex uranyl. The β‐sheet structure is a key parameter to get high stability, because it orients the coordinating carboxylate groups of four amino acid side chains in the equatorial plane of the dioxo cation.