title: Preorganized Peptide Scaffolds as Mimics of Phosphorylated Proteins Binding Sites with a High Affinity for Uranyl.
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 10(10) at physiological pH. These compounds are therefore promising models for understanding uranyl chelation by proteins, which is relevant to this actinide ion toxicity.
authors.affiliation: Université Grenoble Alpes , INAC-SCIB, F-38000 Grenoble, France.|CEA , INAC-SCIB, F-38000 Grenoble, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Starck
authors.affiliation: Université Grenoble Alpes , INAC-SCIB, F-38000 Grenoble, France.|CEA , INAC-SCIB, F-38000 Grenoble, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sisommay
authors.affiliation: Université Grenoble Alpes , INAC-SCIB, F-38000 Grenoble, France.|CEA , INAC-SCIB, F-38000 Grenoble, France.
authors.forename: Fanny A
authors.initials: FA
authors.lastname: Laporte
authors.affiliation: Université Grenoble Alpes , INAC-SCIB, F-38000 Grenoble, France.|CEA , INAC-SCIB, F-38000 Grenoble, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oros
authors.affiliation: Université Grenoble Alpes , INAC-SCIB, F-38000 Grenoble, France.|CEA , INAC-SCIB, F-38000 Grenoble, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Lebrun
authors.affiliation: Université Grenoble Alpes , INAC-SCIB, F-38000 Grenoble, France.|CEA , INAC-SCIB, F-38000 Grenoble, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Delangle
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002942:Circular Dichroism; D018698:Glutamic Acid / Q000737:chemistry; D007098:Imino Acids; D018716:Molecular Mimicry; D053495:Osteopontin / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D010748:Phosphopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010768:Phosphoserine / Q000737:chemistry; D017433:Protein Structure, Secondary; D021241:Spectrometry, Mass, Electrospray Ionization; D014364:Tryptophan / Q000737:chemistry; D014502:Uranyl Nitrate / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D007098:Imino Acids; D010456:Peptides, Cyclic; D010748:Phosphopeptides; D014502:Uranyl Nitrate; D053495:Osteopontin; D010768:Phosphoserine; D018698:Glutamic Acid; D014364:Tryptophan; D002118:Calcium; C008109:iminodiacetic acid