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Evaluation of enzymatic and magnetic properties of γ-glutamyl-[1-(13)C]glycine and its deuteration toward longer retention of the hyperpolarized state
Dynamic nuclear polarization (DNP) is an emerging cutting-edge method of acquiring metabolic and physiological information in vivo. We recently developed γ-glutamyl-[1-(13)C]glycine (γ-Glu-[1-(13)C]Gly) as a DNP nuclear magnetic resonance (NMR) molecular probe to detect γ-glutamyl transpeptidase (GG...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043577/ https://www.ncbi.nlm.nih.gov/pubmed/35496407 http://dx.doi.org/10.1039/d1ra07343e |
Sumario: | Dynamic nuclear polarization (DNP) is an emerging cutting-edge method of acquiring metabolic and physiological information in vivo. We recently developed γ-glutamyl-[1-(13)C]glycine (γ-Glu-[1-(13)C]Gly) as a DNP nuclear magnetic resonance (NMR) molecular probe to detect γ-glutamyl transpeptidase (GGT) activity in vivo. However, the detailed enzymatic and magnetic properties of this probe remain unknown. Here, we evaluate a γ-Glu–Gly scaffold and develop a deuterated probe, γ-Glu-[1-(13)C]Gly-d(2), that can realize a longer lifetime of the hyperpolarized signal. We initially evaluated the GGT-mediated enzymatic conversion of γ-Glu–Gly and the magnetic properties of (13)C-enriched γ-Glu–Gly (γ-Glu-[1-(13)C]Gly and γ-[5-(13)C]Glu–Gly) to support the validity of γ-Glu-[1-(13)C]Gly as a DNP NMR molecular probe for GGT. We then examined the spin-lattice relaxation time (T(1)) of γ-Glu-[1-(13)C]Gly and γ-Glu-[1-(13)C]Gly-d(2) under various conditions (D(2)O, PBS, and serum) and confirmed that the T(1) of γ-Glu-[1-(13)C]Gly and γ-Glu-[1-(13)C]Gly-d(2) was maintained for 30 s (9.4 T) and 41 s (9.4 T), respectively, even in serum. Relaxation analysis of γ-Glu-[1-(13)C]Gly revealed a significant contribution of the dipole–dipole interaction and the chemical shift anisotropy relaxation pathway (71% of the total relaxation rate at 9.4 T), indicating the potential of deuteration and the use of a lower magnetic field for realizing a longer T(1). In fact, by using γ-Glu-[1-(13)C]Gly-d(2) as a DNP probe, we achieved longer retention of the hyperpolarized signal at 1.4 T. |
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