Fluorescent small-molecule agonists as follicle-stimulating hormone receptor imaging tools,RSC Chemical Biology

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Fluorescent small-molecule agonists as follicle-stimulating hormone receptor imaging tools
RSC Chemical Biology ( IF 4.2 ) Pub Date : 2020-08-03 , DOI: 10.1039/d0cb00068j
Sascha Hoogendoorn ₁ , Gijs H M van Puijvelde ₂ , Gijs A van der Marel ₁ , Chris J van Koppen ₃ , C Marco Timmers ₄ , Herman S Overkleeft ₁

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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.

中文翻译：

荧光小分子激动剂作为促卵泡激素受体成像工具

荧光细胞表面受体激动剂可以使受体激活所启动的过程可视化。本研究描述了基于二氢吡啶 (DHP) 激动剂的促卵泡激素受体 (FSHR) 的两种荧光低分子量配体的合成。我们表明 BODIPY 和 Cy5 偶联的 DHP（m -DHP-BDP 和m -DHP-Cy5）都是有效的 FSHR 激动剂，能够以纳摩尔强度激活受体信号传导，并在更高浓度下影响受体内化。的FSHR依赖性摄取米-DHP-Cy5的是形成鲜明对比的细胞摄取米-DHP-BDP 在没有 FSHR 的情况下也能有效内化。我们的结果包括用于原位FSHR 成像的一流荧光低分子量配体，并涉及将药物靶向递送到表达 FSHR 的细胞的内溶酶体途径中的潜在手段。

更新日期：2020-10-08

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