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A series of novel fluorescent agonists were well developed herein with turn-on switch for α1-adrenergic receptors (α1-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 α1-ARs. Moreover, these probes have been successfully applied for selectively imaging α1-ARs in the living cells. The dynamic process of α1-ARs internalization was traced successfully with these newly designed fluorescent agonists. Fluorescence polarization assay demonstrated specific interactions between these probes and α1-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 α1-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 α1-ARs during drug discovery.

As a neurotransmitter, norepinephrine (NE) is critical for psychiatric conditions, neurodegenerative diseases, and pheochromocytoma. A real-time and noninvasive method for the detection of NE as a tracer to investigate the NE-relevant disease treatment process is urgently desirable. Herein, we successfully developed a turn-on NE bioluminescent probe (NBP), which was grounded on p-toluenethiol deprotectrf by nucleophilic substitution. Compared with other analytes, the NBP exhibited high sensitivity and selectivity in vitro. More importantly, the NBP provides a promising strategy for in vivo imaging of NE in living animals with noninvasive visualization and real-time features.

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