Hyperpolarization is a highly promising technique for improving the sensitivity of magnetic resonance chemical probes. Here we report [15N, D9]trimethylphenylammonium as a platform for designing a variety of hyperpolarized magnetic resonance chemical probes. The platform structure shows a remarkably long 15N spin–lattice relaxation value (816 s, 14.1 T) for retaining its hyperpolarized spin state. The extended lifetime enables the detection of the hyperpolarized 15N signal of the platform for several tens of minutes and thus overcomes the intrinsic short analysis time of hyperpolarized probes. Versatility of the platform is demonstrated by applying it to three types of hyperpolarized chemical probes: one each for sensing calcium ions, reactive oxygen species (hydrogen peroxide) and enzyme activity (carboxyl esterase). All of the designed probes achieve high sensitivity with rapid reactions and chemical shift changes, which are sufficient to allow sensitive and real-time monitoring of target molecules by 15N magnetic resonance.
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.
The g-glutamyl transpeptidase (GGT) enzyme plays ac entral role in glutathione homeostasis.D irect detection of GGT activity could provide critical information for the diagnosis of several pathologies.W epropose anew molecular probe, g-Glu-[1-13 C]Gly,f or monitoring GGT activity in vivo by hyperpolarized (HP) 13 Cm agnetic resonance (MR). The properties of g-Glu-[1-13 C]Gly are suitable for in vivo HP 13 C metabolic analysis since the chemical shift between g-Glu-[1-13 C]Gly and its metabolic product, [1-13 C]Gly,i sl arge (4.3 ppm) and the T 1 of both compounds is relatively long (30 sa nd 45 s, respectively,i nH 2 Oa t9 .4 T). We also demonstrate that g-Glu-[1-13 C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin.
Hyperpolarization is an emerging method that dramatically enhances NMR signal intensity. As a result of their increased sensitivity, hyperpolarized (HP) NMR molecular probes can be used to perform time-resolved spectroscopy and imaging in vitro and in vivo. It is, however, challenging to design such probes de novo. Herein, the [1- C]α-amino acid is reported as a scaffold structure to design HP C NMR molecular probes. The [1- C]α-amino acid can be converted to various HP C chemical probes that show sufficient chemical shift change by altering the chemical state of the α nitrogen upon interaction with the target. Several previously reported HP probes could be explained by this design principle. To demonstrate the versatility of this approach, two α-amino-acid-based HP C chemical probes, sensitive to pH and Ca ion, were developed and used to detect targets.
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