Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay
Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan
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Academic Editor: Manuel Vázquez-Carrera
Int. J. Mol. Sci. 2021, 22(8), 4034; https://doi.org/10.3390/ijms22084034
Received: 27 March 2021
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Revised: 10 April 2021
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Accepted: 11 April 2021
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Published: 14 April 2021
(This article belongs to the Special Issue PPARs as Key Mediators of Metabolic and Inflammatory Regulation)
Peroxisome proliferator-activated receptor γ (PPARγ) is a molecular target of metabolic syndrome and inflammatory disease. PPARγ is an important nuclear receptor and numerous PPARγ ligands were developed to date; thus, efficient assay methods are important. Here, we investigated the incorporation of 7-diethylamino coumarin into the PPARγ agonist rosiglitazone and used the compound in a binding assay for PPARγ. PPARγ-ligand-incorporated 7-methoxycoumarin, 1, showed weak fluorescence intensity in a previous report. We synthesized PPARγ-ligand-incorporating coumarin, 2, in this report, and it enhanced the fluorescence intensity. The PPARγ ligand 2 maintained the rosiglitazone activity. The obtained partial agonist 6 appeared to act through a novel mechanism. The fluorescence intensity of 2 and 6 increased by binding to the ligand binding domain (LBD) of PPARγ and the affinity of reported PPARγ ligands were evaluated using the probe.
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Keywords:
PPARγ ligand; coumarin; fluorescent ligand; screening; crystal structure
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MDPI and ACS Style
Yoshikawa, C.; Ishida, H.; Ohashi, N.; Itoh, T. Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay. Int. J. Mol. Sci. 2021, 22, 4034. https://doi.org/10.3390/ijms22084034
AMA Style
Yoshikawa C, Ishida H, Ohashi N, Itoh T. Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay. International Journal of Molecular Sciences. 2021; 22(8):4034. https://doi.org/10.3390/ijms22084034
Chicago/Turabian StyleYoshikawa, Chisato, Hiroaki Ishida, Nami Ohashi, and Toshimasa Itoh. 2021. "Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay" International Journal of Molecular Sciences 22, no. 8: 4034. https://doi.org/10.3390/ijms22084034
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