Fluorescent small-molecule agonists as follicle-stimulating hormone receptor imaging tools.
Fluorescent small-molecule agonists as follicle-stimulating hormone receptor imaging tools.
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DOI：
10.1039/d0cb00068j
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发表时间：
2020-10-01
影响因子：
4.1
通讯作者：
Overkleeft HS
中科院分区：
文献类型：
--
作者：
Hoogendoorn S;van Puijvelde GHM;van der Marel GA;van Koppen CJ;Timmers CM;Overkleeft HS
荧光细胞表面受体激动剂允许通过受体激活而启动的过程的可视化。本研究描述了基于二氢吡啶（DHP）激动剂的卵泡刺激素受体（FSHR）的两种荧光低分子量配体的合成。我们表明，BODIPY-和Cy 5-缀合的DHP（m-DHP-BDP和m-DHP-Cy 5）都是有效的FSHR激动剂，能够以纳摩尔效力激活受体信号传导，并在较高浓度下影响受体内化。m-DHP-Cy 5的FSHR依赖性摄取与m-DHP-BDP的细胞摄取形成鲜明对比，m-DHP-BDP在不存在FSHR的情况下也被有效内化。我们的研究结果包括一流的荧光低分子量的配体在原位FSHR成像和有关的潜在手段，有针对性地将药物输送到内溶酶体途径的FSHR表达细胞。发现一种有效的小分子促卵泡激素受体（FSHR）荧光激动剂，用于FSHR表达细胞的选择性染色。
Fluorescent cell surface receptor agonists allow visualization of processes that are set in motion by receptor activation. This study describes the synthesis of two fluorescent, low molecular weight ligands for the follicle-stimulating hormone receptor (FSHR), based on a dihydropyridine (DHP) agonist. We show that both BODIPY- and Cy5-conjugated DHP (m-DHP-BDP and m-DHP-Cy5) are potent FSHR agonists, able to activate receptor signalling with nanomolar potencies and to effect receptor internalisation at higher concentrations. FSHR-dependent uptake of m-DHP-Cy5 is in stark contrast to the cellular uptake of m-DHP-BDP which was efficiently internalised also in the absence of FSHR. Our results comprise a first-in-class fluorescent low molecular weight ligand for in situ FSHR imaging and pertain the potential means for targeted delivery of drugs into the endolysosomal pathway of FSHR-expressing cells. Discovery of a potent, small-molecule, fluorescent agonist of the follicle-stimulating hormone receptor (FSHR) for selective staining of FSHR-expressing cells.