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Poster Presentations
Day 2, June 23（Mon.）
Room P (Maesato East, Foyer, Ocean Wing)
- 2P-PM-24
An analytical platform for the comprehensive and efficient discovery of metabolite ligands for orphan receptors
(1MIB, Kyushu Univ., 2SLS, Kyushu Univ., 3RIMD, Osaka Univ.)
oKeisuke Nakata1, Masatomo Takahashi1,2, Taihei Torigoe1, Noriyuki Tomiyasu1,2, Kosuke Hata1, Sho Yamasaki3, Takeshi Bamba1,2, Yoshihiro Izumi1,2
Metabolites act as ligand molecules that regulate biological activities through interactions with macromolecules, such as nucleic acids and proteins. While liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) has advanced metabolomics by detecting thousands of molecular features in biological samples, more than 80% remain unidentified, including potential ligands for orphan receptors, such as immune and G protein-coupled receptors. Identification of these ligands is essential for understanding immune regulation and developing novel therapeutics; however, this process is limited by analytical sensitivity, structural elucidation, and receptor-ligand interaction screening. To address these challenges, we have developed an integrated LC-HRMS/MS and microfractionation system (LC-FRC-HRMS/MS) that enables efficient ligand screening using cell reporter assays in a 96-well plate. In this study, we solved the technical problems of the previous system by optimizing the chromatographic separation and ionization conditions, such as increasing the column size, increasing the injection volume, and reducing particle size. In addition, by fine-tuning the split ratio between FRC and MS, we mitigated the loss of sensitivity and improved the throughput for hydrophobic and hydrophilic metabolite ligands. This platform is expected to facilitate ligand discovery and be useful not only for immune receptors but also for functional food research and traditional medicine applications.