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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 contras

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Assfalg M,Gianolio E,Zanzoni S,Tomaselli S,Russo VL,Cabella C,Ragona L,Aime S,Molinari H

doi

10.1021/jm070397i

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

5257-68

issue

22

eissn

0022-2623

issn

1520-4804

journal_volume

50

pub_type

杂志文章

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