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

Autor: Kondo Y; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., Saito Y; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., Seki T; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Takakusagi Y; Quantum Hyperpolarized MRI Research Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Anagawa 4-9-1, Inage, Chiba-city 263-8555, Japan.; Institute for Quantum Medical Science (iQMS), National Institutes for Quantum Science and Technology (QST), Anagawa 4-9-1, Inage, Chiba-city 263-8555, Japan.; Department of Quantum Life Science, Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage, Chiba-city 265-8522, Japan., Koyasu N; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Saito K; Quantum Hyperpolarized MRI Research Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Anagawa 4-9-1, Inage, Chiba-city 263-8555, Japan., Morimoto J; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., Nonaka H; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan., Miyanishi K; Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.; Center for Quantum Information and Quantum Biology, Osaka University, Osaka 560-8531, Japan., Mizukami W; Center for Quantum Information and Quantum Biology, Osaka University, Osaka 560-8531, Japan., Negoro M; Quantum Hyperpolarized MRI Research Team, Quantum Life Spin Group, Institute for Quantum Life Science (iQLS), National Institutes for Quantum Science and Technology (QST), Anagawa 4-9-1, Inage, Chiba-city 263-8555, Japan.; Center for Quantum Information and Quantum Biology, Osaka University, Osaka 560-8531, Japan.; Premium Research Institute for Human Metaverse Medicine, Osaka University, Toyonaka, Osaka 560-0043, Japan., Elhelaly AE; Department of Radiology, Frontier Science for Imaging, School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan., Hyodo F; Department of Pharmacology, School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.; Center for One Medicine Innovative Translational Research (COMIT), Gifu University, 501-1194, Gifu, Japan., Matsuo M; Department of Radiology, School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan., Raju N; Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD 20850, USA., Swenson RE; Chemistry and Synthesis Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD 20850, USA., Krishna MC; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Yamamoto K; Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Sando S; Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.; Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Oct 18; Vol. 10 (42), pp. eadp2533. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1126/sciadv.adp2533
Abstrakt: 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 ( T 1 ). Because of the limitation in T 1 , 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 13 C-oligopeptides. Structure-based T 1 relaxation analysis suggests that the C-terminal [1- 13 C]Gly- d 2 residue affords sufficient T 1 for biological uses, even in relatively large oligopeptides, and allowed us to develop 13 C-β-casomorphin-5 and 13 C-glutathione. It was found that the metabolic response and perfusion of the hyperpolarized 13 C-glutathione in the mouse kidney were significantly altered in a model of cisplatin-induced acute kidney injury.
Databáze: MEDLINE