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2006-05-15 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Henoumont Céline , Henrotte Virginie, Laurent Sophie , Vander Elst Luce , Muller Robert , "Investigation of non covalent interactions between lanthanides complexes and proteins by proton relaxometry and NMR diffusometry" in Journée de l'école doctorale en sciences pharmaceutiques, Université de Bruxelles (ULB), Belgique, 2006

  • Codes CREF : Résonance magnétique nucléaire (biophysique) (DI131B)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé), Institut des Biosciences (Biosciences)

Abstract(s) :

(Anglais) The research in the field of contrast agent for magnetic resonance imaging focuses nowadays on the development of specific compounds for molecular imaging. To this end, part of our research deals with the elaboration of gadolinium agents interacting with biomolecules in order to increase its efficacy and its vascular lifetime, both effects are of paramount importance in the field of molecular imaging. In this context, interaction of small Gd complexes with human serum albumin (HSA) has been chosen as a model system. Various techniques, like ultrafiltration [1], mass spectrometry [2], and NMR spectroscopy [3] have proved their efficacy for measuring this type of non covalent binding. We have used two complementary techniques : - Proton relaxometry which consists in measuring the water longitudinal relaxation rate in the presence of HSA 4% and of various ligand concentrations. This method gives rapid information on the affinity for HSA but the estimation of the association constants can be ambiguous because of the large number of undetermined parameters. - NMR diffusometry which consists in the study of the variation of the ligand diffusion coefficient in the absence and in the presence of HSA. One problem of this method, well known in the literature, is the presence of the background of the HSA signals, hiding the peaks of interest. To avoid this, europium complexes were chosen since this lanthanide is well known for its large induced shifts, so that the signals of the complexes are shifted outside the HSA’s background. The feasibility of the technique has been first tested on three complexes, which affinity for HSA is well-known in the literature. The results prompted us to extend the study on three new complexes, synthesized recently in our laboratory. This method seems suitable for the study of complexes showing weak or medium affinity for HSA but for too strong interactions no variation of the diffusion coefficient is observed because of a slow exchange between bound and free ligand. [1] Caravan P., Cloutier N.J., Greenfield M.T., McDermid S.A., Dunham S.U., Bulte J.W.M., Amedio J.C., Looby R.J., Supkowski R.M., Horrocks W.D., McMurry T.J., Lauffer R.B., « The interaction of MS-325 with Human Serum Albumin and Its Effect on Proton Relaxation Rates », J.Am.Chem.Soc. 124 (12) 3152-3162 (2002) [2] Henrotte V., Laurent S., Gabelica V., Vander Elst L., De Pauw E., Muller RN., « Investigation of non-covalent interactions between paramagnetic complexes and human serum albumin by electrospray mass spectrometry », Rap. Comm. Mass Spectrom. 18 (17): 1919-1924 (2004) [3] Lepre C.A., Moore J.M., Peng J.W., « Theory and Applications of NMR-Based Screening in Pharmaceutical Research », Chem. Rev., 104, 3641-3675 (2004)