Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay
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...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/8/4034 |
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| author | Chisato Yoshikawa Hiroaki Ishida Nami Ohashi Toshimasa Itoh |
| author_facet | Chisato Yoshikawa Hiroaki Ishida Nami Ohashi Toshimasa Itoh |
| author_sort | Chisato Yoshikawa |
| collection | DOAJ |
| description | 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, <b>1</b>, showed weak fluorescence intensity in a previous report. We synthesized PPARγ-ligand-incorporating coumarin, <b>2</b>, in this report, and it enhanced the fluorescence intensity. The PPARγ ligand <b>2</b> maintained the rosiglitazone activity. The obtained partial agonist <b>6</b> appeared to act through a novel mechanism. The fluorescence intensity of <b>2</b> and <b>6</b> increased by binding to the ligand binding domain (LBD) of PPARγ and the affinity of reported PPARγ ligands were evaluated using the probe. |
| first_indexed | 2024-03-10T12:20:25Z |
| format | Article |
| id | doaj.art-8d87543d0b9a46578e72dfbae7f87a44 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:20:25Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8d87543d0b9a46578e72dfbae7f87a442023-11-21T15:33:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228403410.3390/ijms22084034Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding AssayChisato Yoshikawa0Hiroaki Ishida1Nami Ohashi2Toshimasa Itoh3Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, JapanLaboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, JapanLaboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, JapanLaboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, JapanPeroxisome 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, <b>1</b>, showed weak fluorescence intensity in a previous report. We synthesized PPARγ-ligand-incorporating coumarin, <b>2</b>, in this report, and it enhanced the fluorescence intensity. The PPARγ ligand <b>2</b> maintained the rosiglitazone activity. The obtained partial agonist <b>6</b> appeared to act through a novel mechanism. The fluorescence intensity of <b>2</b> and <b>6</b> increased by binding to the ligand binding domain (LBD) of PPARγ and the affinity of reported PPARγ ligands were evaluated using the probe.https://www.mdpi.com/1422-0067/22/8/4034PPARγ ligandcoumarinfluorescent ligandscreeningcrystal structure |
| spellingShingle | Chisato Yoshikawa Hiroaki Ishida Nami Ohashi Toshimasa Itoh Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay International Journal of Molecular Sciences PPARγ ligand coumarin fluorescent ligand screening crystal structure |
| title | Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay |
| title_full | Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay |
| title_fullStr | Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay |
| title_full_unstemmed | Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay |
| title_short | Synthesis of a Coumarin-Based PPARγ Fluorescence Probe for Competitive Binding Assay |
| title_sort | synthesis of a coumarin based pparγ fluorescence probe for competitive binding assay |
| topic | PPARγ ligand coumarin fluorescent ligand screening crystal structure |
| url | https://www.mdpi.com/1422-0067/22/8/4034 |
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