Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543, Japan.
Int J Mol Sci. 2021 Apr 14;22(8):4034. doi: 10.3390/ijms22084034.
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, , showed weak fluorescence intensity in a previous report. We synthesized PPARγ-ligand-incorporating coumarin, , in this report, and it enhanced the fluorescence intensity. The PPARγ ligand maintained the rosiglitazone activity. The obtained partial agonist appeared to act through a novel mechanism. The fluorescence intensity of and increased by binding to the ligand binding domain (LBD) of PPARγ and the affinity of reported PPARγ ligands were evaluated using the probe.
过氧化物酶体增殖物激活受体 γ (PPARγ) 是代谢综合征和炎症性疾病的分子靶点。PPARγ 是一种重要的核受体，迄今为止已经开发出许多 PPARγ 配体；因此，高效的检测方法非常重要。在这里，我们研究了 7-二乙氨基香豆素与 PPARγ 激动剂罗格列酮的结合，并将该化合物用于 PPARγ 的结合测定。在之前的报道中，PPARγ-配体结合的 7-甲氧基香豆素， 显示出较弱的荧光强度。我们在本报告中合成了结合香豆素的 PPARγ-配体， ，它增强了荧光强度。PPARγ 配体 保持了罗格列酮的活性。所得到的部分激动剂 似乎通过一种新的机制起作用。荧光强度的 和 通过与 PPARγ 的配体结合域 (LBD) 结合而增加，并用探针评估了报告的 PPARγ 配体的亲和力。
