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Study of non-covalent interactions between MRI contrast agents and human serum albumin by NMR diffusometry

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Abstract

The NMR diffusometry technique, based on the measurement of the diffusion coefficient of a ligand in the absence and in the presence of its macromolecular partner, was used to study the affinity for human serum albumin (HSA) of four gadolinium complexes, potential or already used magnetic resonance imaging contrast agents. Diamagnetic lanthanum(III) ion or europium(III) ion, which has the advantage of shifting the NMR signals far away from those of the macromolecule, was used to avoid the excessive broadening of the NMR signals induced by the gadolinium(III) ion. Titration experiments, in which the HSA concentration was kept constant and the concentration of the europium or lanthanum chelate was varied, were performed to evaluate the association constant and the number of binding sites. Some additional information about the kinetics of the exchange between the free and the bound chelate was also obtained. Competition experiments with ibuprofen and salicylate, which are ligands with a known affinity for the macromolecule and for which the binding site is known, were also performed to get information about the binding site of the contrast agents.

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Acknowledgments

The authors thank Patricia de Francisco for her help in preparing the manuscript. This work was supported by the FNRS and the ARC Program 05/10-335 of the French Community of Belgium. The support and sponsorship accorded by COST Action D38 and EMIL NoE of the FP6 of the EC are kindly acknowledged.

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Authors and Affiliations

  1. NMR and Molecular Imaging Laboratory, Department of General, Organic and Biomedical Chemistry, University of Mons-Hainaut, 24 Avenue du Champ de Mars, 7000, Mons, Belgium

    C. Henoumont, L. Vander Elst, S. Laurent & Robert N. Muller

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  1. C. Henoumont
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  2. L. Vander Elst
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  3. S. Laurent
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  4. Robert N. Muller
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Correspondence to Robert N. Muller.

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Henoumont, C., Vander Elst, L., Laurent, S. et al. Study of non-covalent interactions between MRI contrast agents and human serum albumin by NMR diffusometry. J Biol Inorg Chem 14, 683–691 (2009). https://doi.org/10.1007/s00775-009-0481-0

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  • DOI: https://doi.org/10.1007/s00775-009-0481-0

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