Directly monitoring the dynamic in vivo metabolisms of hyperpolarized <sup>13</sup> C-oligopeptides

Peptides play essential roles in biological phenomena, and, thus, there is a growing interest in detecting in vivo dynamics of peptide metabolisms. Dissolution-dynamic nuclear polarization (d-DNP) is a state-of-the-art technology that can markedly enhance the sensitivity of nuclear magnetic resonance (NMR), providing metabolic and physiological information in vivo. However, the hyperpolarized state exponentially decays back to the thermal equilibrium, depending on the spin-lattice relaxation time (<i>T</i><sub>1</sub>). Because of the limitation in <i>T</i><sub>1</sub>, peptide-based DNP NMR molecular probes applicable in vivo have been limited to amino acids or dipeptides. Here, we report the direct detection of in vivo metabolic conversions of hyperpolarized <sup>13</sup>C-oligopeptides. Structure-based <i>T</i><sub>1</sub> relaxation analysis suggests that the C-terminal [1-<sup>13</sup>C]Gly-<i>d</i><sub>2</sub> residue affords sufficient <i>T</i><sub>1</sub> for biological uses, even in relatively large oligopeptides, and allowed us to develop <sup>13</sup>C-β-casomorphin-5 and <sup>13</sup>C-glutathione. It was found that the metabolic response and perfusion of the hyperpolarized <sup>13</sup>C-glutathione in the mouse kidney were significantly altered in a model of cisplatin-induced acute kidney injury.

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Journal
Science Advances
Published
2024-10-16
DOI
https://doi.org/10.1126/sciadv.adp2533
Citations
5
Primary Topic
Advanced NMR Techniques and Applications
Type
article
Field-Weighted Citation Impact
1.20
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article

Directly monitoring the dynamic in vivo metabolisms of hyperpolarized 13 C-oligopeptides

Shinsuke Sando, Yoichi Takakusagi, Hiroshi Nonaka, Jumpei Morimoto et al.
5 citations
Science Advances
Advanced NMR Techniques and Applications
1.20
article

Directly monitoring the dynamic in vivo metabolisms of hyperpolarized 13 C-oligopeptides

Shinsuke Sando, Yoichi Takakusagi, Hiroshi Nonaka, Jumpei Morimoto, Masayuki Matsuo, Norikazu Koyasu, Abdelazim Elsayed Elhelaly, Namboori B. Raju, Kazutoshi Yamamoto, Rolf E. Swenson, Wataru Mizukami, Yohei Kondo, Yutaro Saito, Makoto Negoro, Koichiro Miyanishi, Fuminori Hyodo, Tomohiro Seki, Keita Saito, Murali C. Krishna
article en
5 citations

Abstract

Peptides play essential roles in biological phenomena, and, thus, there is a growing interest in detecting in vivo dynamics of peptide metabolisms. Dissolution-dynamic nuclear polarization (d-DNP) is a state-of-the-art technology that can markedly enhance the sensitivity of nuclear magnetic resonance (NMR), providing metabolic and physiological information in vivo. However, the hyperpolarized state exponentially decays back to the thermal equilibrium, depending on the spin-lattice relaxation time (<i>T</i><sub>1</sub>). Because of the limitation in <i>T</i><sub>1</sub>, peptide-based DNP NMR molecular probes applicable in vivo have been limited to amino acids or dipeptides. Here, we report the direct detection of in vivo metabolic conversions of hyperpolarized <sup>13</sup>C-oligopeptides. Structure-based <i>T</i><sub>1</sub> relaxation analysis suggests that the C-terminal [1-<sup>13</sup>C]Gly-<i>d</i><sub>2</sub> residue affords sufficient <i>T</i><sub>1</sub> for biological uses, even in relatively large oligopeptides, and allowed us to develop <sup>13</sup>C-β-casomorphin-5 and <sup>13</sup>C-glutathione. It was found that the metabolic response and perfusion of the hyperpolarized <sup>13</sup>C-glutathione in the mouse kidney were significantly altered in a model of cisplatin-induced acute kidney injury.

Science AdvancesVol. 10(42)
National Institutes of Health (US), Chiba University (JP), National Heart, Lung, and Blood Institute (US), National Institutes for Quantum Science and Technology (JP), National Cancer Institute (US), Center for Cancer Research (US), Gifu University (JP), The University of Tokyo (JP), The University of Osaka (JP)
Openalex Percentile: Top 23%
Advanced NMR Techniques and Applications
1.20
DOIOpen Access PDFOpenAlex
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