Development and Characterization of a Highly Selective Turn-On Fluorescent Ligand for β3-Adrenergic Receptor

被引:6
作者
Li, Wenhua [1 ]
Ma, Zhao [1 ]
Du, Lupei [1 ]
Li, Minyong [1 ]
机构
[1] Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Dept Med Chem,Key Lab Chem Biol MOE, Jinan 250012, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
BETA-ADRENERGIC-RECEPTORS; MESSENGER-RNA; BETA(3)-ADRENOCEPTOR; DISCOVERY; MICROENVIRONMENT; ADRENOCEPTOR; PHARMACOLOGY; EXPRESSION; BINDING; TARGET;
D O I
10.1021/acs.analchem.2c04269
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
For the precise visualization of GPCR, subtype selectivity of turn-on fluorescent ligands is of major relevance. Although there are many thriving fl-adrenergic receptors (fl-ARs) probes, none of them are selective to the fl3-subtype, which severely limits the development of fl3-AR investigations. Using a polyethylene glycol (PEG) chain to conjugate the Py-5 fluorophore with mirabegron, we present here a highly selective fluorescent ligand, H2, for fl3-AR. It was established by the radioligand and NanoLuc-based bioluminescence resonance energy transfer (NanoBRET) binding experiments that molecule H2 has a substantially higher affinity for fl3-AR than the other two subtypes (1/3, 45-fold; 2/3, 16-fold). More crucially, when molecule H2 was incubated with fl3-AR, the turn-on fluorescent signals could be quickly released. The subsequent investigations, which included cell imaging, tissue imaging, and flow-cytometry analysis, proved that molecule H2 may make it possible to quickly and accurately fluorescently identify fl3-AR at different levels. We offer a prospective fluorescent turn-on ligand with exceptional selectivity for fl3-AR as a result of our combined efforts.
引用
收藏
页码:2848 / 2856
页数:9
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