Discovery of TAS2R14 Agonists from Platycodon grandiflorum Using Virtual Screening and Affinity Screening Based on a Novel TAS2R14-Functionalized HEMT Sensor Combined with UPLC–MS Analysis
2018
Wang, Zhi-Xin | Zhang, Yu-Xin | Zeng, Yan-Ling | Li, Xi | Chen, Zhao | Luo, Jia-Ming | Zhang, Yang | Zhang, Yan-Ling | Qiao, Yan-Jiang
TAS2R14 is of great potential as a therapeutic target against asthma, and the discovery of TAS2R14 agonists can be very valuable for treating this disease. Herein, we developed a strategy using virtual screening and affinity screening based on a fabricated biosensor combined with UPLC–MS analysis to screen TAS2R14 agonists from Platycodon grandiflorum. By ligand-based virtual screening, 16 best-fit candidates were yielded. A novel TAS2R14-functionalized high-electron-mobility transistor (HEMT) sensor was applied to detect and fish out the potential TAS2R14 agonists from P. grandiflorum extracts. Those components captured by the immobilized TAS2R14 were eluted and characterized on UPLC−QTOF MS. As a result, six potential TAS2R14 agonists were screened out and identified. Among them, platycodin L was confirmed to be a special agonist of TAS2R14 for the first time and had an EC₅₀ of 15.03 ± 1.15 μM via intracellular calcium mobilization assay (n = 6). The results indicated that the proposed strategy was efficient to discover TAS2R14 agonists from the herb directly.
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