Development of Fluorescent Ligands for the Human 5-HT1A Receptor

作者：Alonso Dulce; Vazquez Villa Henar; Gamo Ana M; Martinez Esperon Maria F; Tortosa Mariola; Viso Alma; Fernandez de la Pradilla Roberto; Junquera Elena; Aicart Emilio; Martin Fontecha Mar; Benhamu Bellinda; Lopez Rodriguez Maria L^*; Ortega Gutierrez Silvia

来源：ACS Medicinal Chemistry Letters, 2010, 1(6): 249-253.

DOI：10.1021/ml100053y

• G protein-coupled receptors (GPCRs)
• serotonin (5-HT)
• 5-HT1A receptor
• probes
• fluorescent ligands
• receptor visualization

In this work, we report the design and synthesis of a set of fluorescent probes targeting the human 5-HT1A receptor (h5-HT1AR). Among the synthesized compounds, derivative 4 deserves special attention as being a high-affinity ligand (K-i = 2 nM) with good fluorescent properties (I-em > 1000 au and a fluorescence quantum yield, Phi(f), of 0.26), which enables direct observation of the h5-HT1AR in cells. Thus, it represents the first efficacious fluorescent probe for the specific labeling of h5-HT1AR in cells. Our results provide the basis for the introduction of a variety of tags in scaffolds of G protein-coupled receptor(GPCR) ligands that enable visualization, covalent binding, or affinity pull-down of receptors. These strategies should contribute to the optimization of the therapeutic exploitation of known or new members of the GPCR superfamily by providing valuable information about their location or level of expression.

• 出版日期2010-9