{"title":"Directly monitoring the dynamic in vivo metabolisms of hyperpolarized 13C-oligopeptides","authors":"Yohei Kondo, Yutaro Saito, Tomohiro Seki, Yoichi Takakusagi, Norikazu Koyasu, Keita Saito, Jumpei Morimoto, Hiroshi Nonaka, Koichiro Miyanishi, Wataru Mizukami, Makoto Negoro, Abdelazim E. Elhelaly, Fuminori Hyodo, Masayuki Matsuo, Natarajan Raju, Rolf E. Swenson, Murali C. Krishna, Kazutoshi Yamamoto, Shinsuke Sando","doi":"10.1126/sciadv.adp2533","DOIUrl":null,"url":null,"abstract":"<div >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.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":null,"pages":null},"PeriodicalIF":11.7000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adp2533","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/sciadv.adp2533","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
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 (T1). Because of the limitation in T1, 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 13C-oligopeptides. Structure-based T1 relaxation analysis suggests that the C-terminal [1-13C]Gly-d2 residue affords sufficient T1 for biological uses, even in relatively large oligopeptides, and allowed us to develop 13C-β-casomorphin-5 and 13C-glutathione. It was found that the metabolic response and perfusion of the hyperpolarized 13C-glutathione in the mouse kidney were significantly altered in a model of cisplatin-induced acute kidney injury.
期刊介绍:
Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.