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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 Contrast Agent

Supporting Info

Michael Assfalg,^† Eliana Gianolio,^‡ Serena Zanzoni,^† Simona Tomaselli,^§ Vito Lo Russo, Claudia Cabella, Laura Ragona,^§ Silvio Aime,*^‡ and Henriette Molinari*^†

Dipartimento Scientifico e Tecnologico, Universit di Verona, Strada Le Grazie 15, 37134 Verona, Italy, Dipartimento di Chimica, Universit di Torino, Via Pietro Giuria 7, Torino, Italy, ISMAC-CNR, Via Bassini 15, 20133 Milano, Italy, Bracco Imaging SpA, via E. Folli 50, 20134 Milano, Italy, and Bracco Imaging Spa, via Ribes 5, 10010 Colleretto Giacosa (TO), Italy

J. Med. Chem., 2007, 50 (22), pp 5257–5268

DOI: 10.1021/jm070397i

Publication Date (Web): October 4, 2007

†

Università di Verona.

‡

Università di Torino.

ISMAC-CNR.

Bracco Imaging Spa, Milano, Italy.

Bracco Imaging Spa, Colleretto Giacosa (TO), Italy.

To whom correspondence should be addressed. Phone: +39 0116707520 (S.A.); +39 0458027901 (H.M.). Fax: +39 0116707855 (S.A.); +39 0458027929 (H.M.). E-mail: silvio.aime@unito.it (S.A.); molinari@sci.univr.it (H.M.).

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.

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Published In Issue November 01, 2007
Received April 4, 2007

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Article

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

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SciFinder Links

Accession Codes

History

Recommend & Share

Related Content

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Discovery of 1-{2-[(1S)-(3-Dimethylamino-propionyl)amino-2-methylpropyl]-4-methyl-phenyl}-4-[(2R)-methyl-3-(4-chlorophenyl)-propionyl]piperazine as an Orally Active Antagonist of the Melanocortin-4 Receptor for the Potential Treatment of Cachexia

Novel Fluorinated Derivatives of the Broad-Spectrum MMP Inhibitors N-Hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](benzyl)- and (3-picolyl)-amino]-3-methyl-butanamide as Potential Tools for the Molecular Imaging of Activated MMPs with PET

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