title: A gadolinium-binding cyclodecapeptide with a large high-field relaxivity involving second-sphere water.
abstract: A new cyclodecapeptide incorporating two prolylglycine sequences as beta-turn inducers and bearing four side chains with acidic carboxyl groups for cation complexation has been prepared. Structural analysis in water by (1)H NMR spectroscopy and CD shows that this template adopts a conformation suitable for the complexation of lanthanide ions Ln(3+), with its carboxyl groups oriented on the same face of the peptide scaffold. Luminescence titrations show that mononuclear Ln-PA complexes are formed with apparent stability constants of log beta(110) approximately 6.5 (pH 7). The high-field water relaxivity values arising from the Gd-PA complex at 200-500 MHz have been interpreted with molecular parameters determined independently. The experimentally determined water relaxivities are undoubtedly 30% higher than the expected values for this complex with two inner-sphere (IS) water molecules and a medium-range rotational correlation time (tau(R) = 386 ps (+/-10%)). This led us to propose the existence of a large second-sphere (2S) contribution to the relaxivity caused by the interaction of water molecules with the hydrophilic peptide ligand by hydrogen-bonding.
authors.affiliation: INAC, Service de Chimie Inorganique et Biologique (UMR E 3 CEA UJF, FRE CNRS 3200), Commissariat à l'Energie Atomique, 17 rue des martyrs, 38054 Grenoble cedex, France.
authors.forename: Célia S
authors.initials: CS
authors.lastname: Bonnet
authors.forename: Pascal H
authors.initials: PH
authors.lastname: Fries
authors.forename: Serge
authors.initials: S
authors.lastname: Crouzy
authors.forename: Olivier
authors.initials: O
authors.lastname: Sénèque
authors.forename: Federico
authors.initials: F
authors.lastname: Cisnetti
authors.forename: Didier
authors.initials: D
authors.lastname: Boturyn
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.forename: Pascale
authors.initials: P
authors.lastname: Delangle
mesh_terms: D005682:Gadolinium / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry*; D014867:Water
chemical_list: D008024:Ligands; D010456:Peptides, Cyclic; D014867:Water; D005682:Gadolinium