New Fluorescent Adenosine A1-Receptor Agonists That Allow Quantification of Ligand-Receptor Interactions in Microdomains of Single Living Cells

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• 作者：Richard J. Middleton ; Stephen J. Briddon ; Yolande Cordeaux ; Andrew S. Yates ; Clare L. Dale ; Michael W. George ; Jillian. G. Baker ; Stephen J. Hill ; Barrie Kellam
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：February 22, 2007
• 年：2007
• 卷：50
• 期：4
• 页码：782 - 793
• 全文大小：545K
• 年卷期：v.50,no.4(February 22, 2007)
• ISSN：1520-4804

文摘

Fluorescence spectroscopy is becoming a valuable addition to the array of techniques available for scrutinizingligand-receptor interactions in biological systems. In particular, scanning confocal microscopy andfluorescence correlation spectroscopy (FCS) allow the noninvasive imaging and quantification of theseinteractions in single living cells. To address the emerging need for fluorescently labeled ligands to supportthese technologies, we have developed a series of red-emitting agonists for the human adenosine A₁-receptorthat, collectively, are N⁶-aminoalkyl derivatives of adenosine or adenosine 5'-N-ethyl carboxamide. Theagonists, which incorporate the commercially available fluorophore BODIPY [630/650], retain potent andefficacious agonist activity, as demonstrated by their ability to inhibit cAMP accumulation in chinese hamsterovary cells expressing the human adenosine A₁-receptor. Visualization and confirmation of ligand-receptorinteractions at the cell membrane were accomplished using confocal microscopy, and their suitability foruse in FCS was demonstrated by quantification of agonist binding in small areas of cell membrane.