Enzymatically Shifting Nitroxides for EPR Spectroscopy and Overhauser‐Enhanced Magnetic Resonance Imaging. Issue 45 (17th September 2015)

• Record Type: Journal Article
• Authors: Audran, Gérard; Bosco, Lionel; Brémond, Paul; Franconi, Jean‐Michel; Koonjoo, Neha; Marque, Sylvain R. A.; Massot, Philippe; Mellet, Philippe; Parzy, Elodie; Thiaudière, Eric
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 45(2015)
• Page Start: 13379
• Page End: 13384
• Publication Date: 2015-09-17
• Subjects: dynamic nuclear polarization -- enzymes -- nitroxides -- NMR imaging -- Overhauser effect; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201506267
• Languages: English
• ISSNs: 1433-7851

Abstract

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 (Δ a 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. Abstract : Tautomers for in vivo protease imaging : Enzymatically activated nitroxides could be tracked by EPR and an Overhauser‐enhanced MRI technique, permitting imaging of in vivo protease activity in the digestive tract of mice.