Discovery of Environment-Sensitive Fluorescent Agonists for α 1 -Adrenergic Receptors

作者：Xiaojun Qin, Zhao Ma, Xingye Yang, Shilong Hu, Xinxin Chen, Dong Liang, Yuxing Lin, Xiaodong Shi, Lüpei Du, Minyong Li · 发表于：Analytical Chemistry · 年份：2019 · DOI：10.1021/acs.analchem.9b01059 · 被引用次数：22 · 研究领域：Receptor Mechanisms and Signaling、Pharmacological Effects and Assays、Cancer, Stress, Anesthesia, and Immune Response

A series of novel fluorescent agonists were well developed herein with turn-on switch for α 1 -adrenergic receptors (α 1 -ARs) by conjugating the environment-sensitive fluorophore 4-chloro-7-nitrobenzoxadiazole with phenylephrine. Overall, these probes exhibited efficient binding and apparent fluorescence intensity changes (up to 10-fold) upon binding with α 1 -ARs. Moreover, these probes have been successfully applied for selectively imaging α 1 -ARs in the living cells. The dynamic process of α 1 -ARs internalization was traced successfully with these newly designed fluorescent agonists. Fluorescence polarization assay demonstrated specific interactions between these probes and α 1 -ARs. With these new probes, a bioluminescence resonance energy transfer binding assay has been well established and applied to the high-throughput screening of unlabeled α 1 -ARs agonist and antagonist. It is expected that these environment-sensitive fluorescent turn-on agonists may provide useful new tools in studying pharmacology and physiology of α 1 -ARs during drug discovery.