Design, Synthesis, and Assessment of Tricarboxylic Acid Cycle Probes

Area of Science:

• Metabolic Imaging
• Biochemistry
• Chemical Biology

Background:

• Hyperpolarized 13C magnetic resonance spectroscopy offers unique in vivo metabolic activity insights.
• Examining the tricarboxylic acid (TCA) cycle is challenging due to limitations in current hyperpolarized 13C probes.

Purpose of the Study:

• To design novel chemical probes for improved TCA cycle investigation.
• To establish a platform for rapid identification of suitable probe scaffolds for hyperpolarized 13C experiments.

Main Methods:

• Systematic computational analyses.
• Synthetic chemistry techniques.
• In vitro studies to validate probe design.

Main Results:

• A platform was developed for efficient screening of probe scaffolds.
• Two new 13C-labeled chemical probes, [1,4-13C2]-dipropyl succinate and [1,4-13C2]-diallyl succinate, were synthesized.
• The developed probes were successfully employed in hyperpolarized 13C metabolic studies.

Conclusions:

• The developed platform accelerates the design of effective hyperpolarized 13C probes.
• The new succinate-based probes show promise for in vivo TCA cycle metabolic studies.
• This work advances the capabilities of hyperpolarized 13C spectroscopy for metabolic pathway analysis.