title: NMR structural studies of the supramolecular adducts between a liver cytosolic bile acid binding protein and gadolinium(III)-chelates bearing bile acids residues: molecular determinants of the binding of a hepatospecific magnetic resonance imaging contrast agent.
abstract: The binding affinities of a selected series of Gd(III) chelates bearing bile acid residues, potential hepatospecific MRI contrast agents, to a liver cytosolic bile acid transporter, have been determined through relaxivity measurements. The Ln(III) complexes of compound 1 were selected for further NMR structural analysis aimed at assessing the molecular determinants of binding. A number of NMR experiments have been carried out on the bile acid-like adduct, using both diamagnetic Y(III) and paramagnetic Gd(III) complexes, bound to a liver bile acid binding protein. The identified protein "hot spots" defined a single binding site located at the protein portal region. The presented findings will serve in a medicinal chemistry approach for the design of hepatocytes-selective gadolinium chelates for liver malignancies detection.
authors.affiliation: Dipartimento Scientifico e Tecnologico, Università di Verona, Strada Le Grazie 15, 37134 Verona, Italy.
authors.forename: Michael
authors.initials: M
authors.lastname: Assfalg
authors.forename: Eliana
authors.initials: E
authors.lastname: Gianolio
authors.forename: Serena
authors.initials: S
authors.lastname: Zanzoni
authors.forename: Simona
authors.initials: S
authors.lastname: Tomaselli
authors.forename: Vito Lo
authors.initials: VL
authors.lastname: Russo
authors.forename: Claudia
authors.initials: C
authors.lastname: Cabella
authors.forename: Laura
authors.initials: L
authors.lastname: Ragona
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Henriette
authors.initials: H
authors.lastname: Molinari
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000737:chemistry*; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D005682:Gadolinium; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D004369:Pentetic Acid / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; D002614:Chelating Agents; D003287:Contrast Media; D008562:Membrane Glycoproteins; C037643:bile acid binding proteins; D004369:Pentetic Acid; D005682:Gadolinium