Fluorescent ligands for adenosine receptors

• Published in: Bioorganic & medicinal chemistry letters 2013-01, Vol.23 (1), p.26-36
• Main Authors: Kozma, Eszter, Suresh Jayasekara, P., Squarcialupi, Lucia, Paoletta, Silvia, Moro, Stefano, Federico, Stephanie, Spalluto, Giampiero, Jacobson, Kenneth A.
• Format: Article
• Language: English
• Subjects: adenosine; agonists; antagonists; Binding; Boron Compounds - chemistry; chemistry; drugs; energy transfer; flow cytometry; Fluorescein-5-isothiocyanate - chemistry; Fluorescence; fluorescence microscopy; Fluorescent Dyes - chemistry; G protein-coupled receptor; Humans; Ligands; Membrane proteins; Protein Binding; Purine; Purinergic P1 Receptor Agonists - chemistry; Purinergic P1 Receptor Agonists - metabolism; Purinergic P1 Receptor Antagonists - chemistry; Purinergic P1 Receptor Antagonists - metabolism; receptors; Receptors, Purinergic P1 - chemistry; Receptors, Purinergic P1 - metabolism; Screening; spectroscopy
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.10.112

Interest is increasing in developing fluorescent ligands for characterization of adenosine receptors (ARs), which hold a promise of usefulness in the drug discovery process. The size of a strategically labeled AR ligand can be greatly increased after the attachment of a fluorophore. The choice of dye moiety (e.g. Alexa Fluor 488), attachment point and linker length can alter the selectivity and potency of the parent molecule. Fluorescent derivatives of adenosine agonists and antagonists (e.g. XAC and other heterocyclic antagonist scaffolds) have been synthesized and characterized pharmacologically. Some are useful AR probes for flow cytometry, fluorescence correlation spectroscopy, fluorescence microscopy, fluorescence polarization, fluorescence resonance energy transfer, and scanning confocal microscopy. Thus, the approach of fluorescent labeled GPCR ligands, including those for ARs, is a growing dynamic research field.