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We developed a system to detect multiple target biomolecules through sensing motif-tethered oligodeoxynucleotides. DNA-based molecular probes gave the primary amine motif upon reaction with the target biomolecules, glutathione (GSH) and H2O2. After labelling with biotin, the product DNAs were selectively collected to be quantified by qPCR. [ABSTRACT FROM AUTHOR]

The excited state properties of thionated 5‐fluorouridine (2′,3′,5′‐tri‐O‐acetyl‐5‐fluoro‐4‐thiouridine; ta5F4TUrd), synthesized with Lawesson's reagent, have been intensively investigated with nanosecond transient absorption spectroscopy, time‐resolved thermal lensing, near‐infrared emission, and quantum chemical calculation. The intrinsic triplet lifetime of ta5F4TUrd was determined to be 4.2±0.7 μs in acetonitrile, and the formation quantum yield of the excited triplet state was as large as 0.79±0.01. The quenching rate constants of the triplet ta5F4TUrd by the dissolved oxygen molecule and by the self‐quenching process were found to be nearly equal to the diffusion‐controlled rate of acetonitrile. The quantum yield of the singlet molecular oxygen produced through energy transfer between the triplet ta5F4TUrd and the dissolved oxygen, ΦΔ, was successfully determined to be 0.61±0.02 under the oxygen‐saturated condition. From the oxygen concentration dependence of the ΦΔ value, the fraction of triplet ta5F4TUrd quenched by dissolved oxygen which gives rise to the 1O2* formation, SΔ, was successfully obtained to be 0.78±0.01, which was the largest among the thionucleobases and the thionucleosides reported so far. This could be due to the lower energy and/or the ππ* character of the triplet state. [ABSTRACT FROM AUTHOR]

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 [1-13C]α-amino acid is reported as a scaffold structure to design HP 13C NMR molecular probes. The [1-13C]α-amino acid can be converted to various HP 13C 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 13C chemical probes, sensitive to pH and Ca2+ ion, were developed and used to detect targets. [ABSTRACT FROM AUTHOR]

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-[1-13C]Gly, for monitoring GGT activity in vivo by hyperpolarized (HP) 13C magnetic resonance (MR). The properties of γ-Glu-[1-13C]Gly are suitable for in vivo HP 13C metabolic analysis since the chemical shift between γ-Glu-[1-13C]Gly and its metabolic product, [1-13C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s and 45 s, respectively, in H2O at 9.4 T). We also demonstrate that γ-Glu-[1-13C]Gly is highly sensitive to in vivo modulation of GGT activity induced by the inhibitor acivicin. [ABSTRACT FROM AUTHOR]

The excited state properties of thionated 5‐fluorouridine (2′,3′,5′‐tri‐O‐acetyl‐5‐fluoro‐4‐thiouridine; ta5F4TUrd), synthesized with Lawesson's reagent, have been intensively investigated with nanosecond transient absorption spectroscopy, time‐resolved thermal lensing, near‐infrared emission, and quantum chemical calculation. The intrinsic triplet lifetime of ta5F4TUrd was determined to be 4.2±0.7 μs in acetonitrile, and the formation quantum yield of the excited triplet state was as large as 0.79±0.01. The quenching rate constants of the triplet ta5F4TUrd by the dissolved oxygen molecule and by the self‐quenching process were found to be nearly equal to the diffusion‐controlled rate of acetonitrile. The quantum yield of the singlet molecular oxygen produced through energy transfer between the triplet ta5F4TUrd and the dissolved oxygen, ΦΔ, was successfully determined to be 0.61±0.02 under the oxygen‐saturated condition. From the oxygen concentration dependence of the ΦΔ value, the fraction of triplet ta5F4TUrd quenched by dissolved oxygen which gives rise to the 1O2* formation, SΔ, was successfully obtained to be 0.78±0.01, which was the largest among the thionucleobases and the thionucleosides reported so far. This could be due to the lower energy and/or the ππ* character of the triplet state. [ABSTRACT FROM AUTHOR]

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., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

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- 13 C]α-amino acid is reported as a scaffold structure to design HP 13 C NMR molecular probes. The [1- 13 C]α-amino acid can be converted to various HP 13 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 13 C chemical probes, sensitive to pH and Ca 2+ ion, were developed and used to detect targets., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)