Direct Monitoring of γ-Glutamyl Transpeptidase Activity In Vivo Using a Hyperpolarized (13) C-Labeled Molecular Probe

Angew Chem Int Ed Engl. 2016 Aug 26;55(36):10626-9. doi: 10.1002/anie.201603731. Epub 2016 Aug 2.

Abstract

The γ-glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ-Glu-[1-(13) C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) (13) C magnetic resonance (MR). The properties of γ-Glu-[1-(13) C]Gly are suitable for in vivo HP (13) C metabolic analysis since the chemical shift between γ-Glu-[1-(13) C]Gly and its metabolic product, [1-(13) C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2 O at 9.4 T). We also demonstrate that γ-Glu-[1-(13) C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin.

Keywords: NMR spectroscopy; biosensors; dynamic nuclear polarization; hyperpolarization; γ-glutamyl transpeptidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Assays / methods*
  • Enzyme Inhibitors / pharmacology
  • Glutathione / metabolism
  • Isoxazoles / pharmacology
  • Molecular Probes / metabolism
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Rats
  • gamma-Glutamyltransferase / antagonists & inhibitors
  • gamma-Glutamyltransferase / metabolism*

Substances

  • Enzyme Inhibitors
  • Isoxazoles
  • Molecular Probes
  • gamma-Glutamyltransferase
  • Glutathione
  • acivicin