State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, 210009, Nanjing, China.
Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, 210009, Nanjing, China.
Anal Chem. 2022 Aug 2;94(30):10722-10729. doi: 10.1021/acs.analchem.2c01206. Epub 2022 Jul 19.
Farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, is a vital ligand-activated transcriptional factor, which is highly expressed in the liver, intestine, and adrenal gland. However, FXR homeostasis is influenced by many factors, such as diet and circadian rhythm, and the expression of FXR differs in diverse organs. Currently, there is no method to monitor the FXR homeostasis in real time, which restricts us from further investigating the function of FXR under physiological and pathological conditions. In this project, classic FXR agonists were selected to be modified to targeting FXR. The photo-cross-linking diazirine group and alkynyl, a click reaction group, were incorporated to the ligands. Through biorthogonal reaction, fluorophore was linked to the ligands to realize the monitoring of FXR expression in cells.
法尼醇 X 受体 (FXR) 是核受体超家族的成员，是一种重要的配体激活转录因子，在肝脏、肠道和肾上腺中高度表达。然而，FXR 的内环境平衡受到许多因素的影响，如饮食和昼夜节律，并且 FXR 在不同的器官中的表达也不同。目前，还没有实时监测 FXR 内环境平衡的方法，这限制了我们在生理和病理条件下进一步研究 FXR 的功能。在这个项目中，选择了经典的 FXR 激动剂进行修饰，以靶向 FXR。将光交联叠氮基团和炔基（点击反应基团）引入配体中。通过生物正交反应，将荧光团与配体连接起来，实现细胞中 FXR 表达的监测。
