title: Enzymatically Shifting Nitroxides for EPR Spectroscopy and Overhauser-Enhanced Magnetic Resonance Imaging.
abstract: In vivo investigations of enzymatic processes using non-invasive approaches are a long-lasting challenge. Recently, we showed that Overhauser-enhanced MRI is suitable to such a purpose. A β-phosphorylated nitroxide substrate prototype exhibiting keto-enol equilibrium upon enzymatic activity has been prepared. Upon enzymatic hydrolysis, a large variation of the phosphorus hyperfine coupling constant (Δa(P)=4 G) was observed. The enzymatic activities of several enzymes were conveniently monitored by electronic paramagnetic resonance (EPR). Using a 0.2 T MRI machine, in vitro and in vivo OMRI experiments were successfully performed, affording a 1200% enhanced MRI signal in vitro, and a 600% enhanced signal in vivo. These results highlight the enhanced imaging potential of these nitroxides upon specific enzymatic substrate-to-product conversion.
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20 (France). g.audran@univ-amu.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Audran
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20 (France).
authors.forename: Lionel
authors.initials: L
authors.lastname: Bosco
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20 (France). paul.bremond@univ-amu.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Brémond
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS, Case 93, University Bordeaux Segalen, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France). jean-michel.franconi@rmsb.u-bordeaux2.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Franconi
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS, Case 93, University Bordeaux Segalen, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France).
authors.forename: Neha
authors.initials: N
authors.lastname: Koonjoo
authors.affiliation: Aix-Marseille Université, CNRS, ICR, UMR 7273, Case 551, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20 (France). sylvain.marque@univ-amu.fr.
authors.forename: Sylvain R A
authors.initials: SR
authors.lastname: Marque
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS, Case 93, University Bordeaux Segalen, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France).
authors.forename: Philippe
authors.initials: P
authors.lastname: Massot
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS, Case 93, University Bordeaux Segalen, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France). philippe.mellet@rmsb.u-bordeaux2.fr.|INSERM, 33076 Bordeaux Cedex (France). philippe.mellet@rmsb.u-bordeaux2.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Mellet
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS, Case 93, University Bordeaux Segalen, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France).
authors.forename: Elodie
authors.initials: E
authors.lastname: Parzy
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536 CNRS, Case 93, University Bordeaux Segalen, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France). eric.thiaudiere@rmsb.u-bordeaux2.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Thiaudière
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D006868:Hydrolysis; D008279:Magnetic Resonance Imaging; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009589:Nitrogen Oxides; D010447:Peptide Hydrolases
keywords: NMR imaging; Overhauser effect; dynamic nuclear polarization; enzymes; nitroxides