title: Supramolecular Assays for Mapping Enzyme Activity by Displacement-Triggered Change in Hyperpolarized (129)Xe Magnetization Transfer NMR Spectroscopy.
abstract: Reversibly bound Xe is a sensitive NMR and MRI reporter with its resonance frequency being influenced by the chemical environment of the host. Molecular imaging of enzyme activity presents a promising approach for disease identification, but current Xe biosensing concepts are limited since substrate conversion typically has little impact on the chemical shift of Xe inside tailored cavities. Herein, we exploit the ability of the product of the enzymatic reaction to bind itself to the macrocyclic hosts CB6 and CB7 and thereby displace Xe. We demonstrate the suitability of this method to map areas of enzyme activity through changes in magnetization transfer with hyperpolarized Xe under different saturation scenarios.
authors.affiliation: ERC Project BiosensorImaging, Leibniz-Institut für Molekulare Pharmakologie (FMP), Campus BerlinBuch, Robert-Rössle-Strasse 10, 13125 Berlin (Germany).
authors.forename: Matthias
authors.initials: M
authors.lastname: Schnurr
authors.affiliation: BAM Bundesanstalt für Materialforschung und -prüfung, Richard-Willstätter-Strasse 11, 12489 Berlin (Germany).
authors.forename: Jagoda
authors.initials: J
authors.lastname: Sloniec-Myszk
authors.affiliation: ERC Project BiosensorImaging, Leibniz-Institut für Molekulare Pharmakologie (FMP), Campus BerlinBuch, Robert-Rössle-Strasse 10, 13125 Berlin (Germany).
authors.forename: Jörg
authors.initials: J
authors.lastname: Döpfert
authors.affiliation: ERC Project BiosensorImaging, Leibniz-Institut für Molekulare Pharmakologie (FMP), Campus BerlinBuch, Robert-Rössle-Strasse 10, 13125 Berlin (Germany). lschroeder@fmp-berlin.de.
authors.forename: Leif
authors.initials: L
authors.lastname: Schröder
authors.affiliation: Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759 Bremen (Germany). a.hennig@jacobs-university.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hennig
mesh_terms: D001952:Bridged-Ring Compounds / Q000737:chemistry; D002262:Carboxy-Lyases / Q000737:chemistry / Q000378:metabolism*; D003287:Contrast Media / Q000737:chemistry; D004789:Enzyme Activation; D057075:Enzyme Assays; D005456:Fluorescent Dyes / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D057054:Molecular Imaging; D014979:Xenon Isotopes; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
chemical_list: D001952:Bridged-Ring Compounds; D002262:Carboxy-Lyases; D003287:Contrast Media; D005456:Fluorescent Dyes; D007093:Imidazoles; D046911:Macromolecular Substances; D014979:Xenon Isotopes; C454805:cucurbit(6)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils; C021520:lysine decarboxylase
keywords: NMR spectroscopy; cucurbituril; enzymes; supramolecular assays; xenon MRI