Design, Synthesis, and Assessment of Tricarboxylic Acid Cycle Probes

Synthesis Pub Date : 2024-06-12 DOI:10.1055/a-2335-8736
Joseph Chen, Darrian Chao, Uyen Phuong Tran, Kelvin L. Billingsley
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Abstract

Hyperpolarized 13C magnetic resonance spectroscopy can provide unique insights into metabolic activity in vivo. Despite the advantages of this technology, certain metabolic pathways such as the tricarboxylic acid (TCA) cycle are more challenging to examine due to the limitations associated with currently available hyperpolarized 13C probes. In this report, we systematically employ computational analyses, synthetic techniques, and in vitro studies to facilitate the design of new chemical probes for the TCA cycle. This platform allows for the rapid identification of probe scaffolds that are amenable to hyperpolarized 13C experimentation. Using these results, we have developed two 13C-labeled chemical probes, [1,4-13C2]-dipropyl succinate and [1,4-13C2]-diallyl succinate, which are employed in hyperpolarized 13C metabolic studies.

Abstract Image

三羧酸循环探针的设计、合成和评估
超极化 13C 磁共振波谱能为了解体内代谢活动提供独特的视角。尽管这项技术具有诸多优势,但由于目前可用的超极化 13C 探针存在局限性,某些代谢途径(如三羧酸(TCA)循环)的研究更具挑战性。在本报告中,我们系统地采用了计算分析、合成技术和体外研究来促进 TCA 循环新化学探针的设计。通过这一平台,我们可以快速确定适合超极化 13C 实验的探针支架。利用这些成果,我们开发出了两种 13C 标记的化学探针,即琥珀酸[1,4-13C2]-二丙酯和琥珀酸[1,4-13C2]-二烯丙基酯,用于超极化 13C 代谢研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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