title: Development of Fluorescent Ligands for the Human 5-HT1A Receptor.
abstract: 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, Φf, 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.
authors.affiliation: Departamento de Química Orgánica I.
authors.forename: Dulce
authors.initials: D
authors.lastname: Alonso
authors.affiliation: Departamento de Química Orgánica I.
authors.forename: Henar
authors.initials: H
authors.lastname: Vázquez-Villa
authors.affiliation: Departamento de Química Orgánica I.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gamo
authors.affiliation: Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, E-28006 Madrid, Spain.
authors.forename: María F
authors.initials: MF
authors.lastname: Martínez-Esperón
authors.affiliation: Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, E-28006 Madrid, Spain.
authors.forename: Mariola
authors.initials: M
authors.lastname: Tortosa
authors.affiliation: Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, E-28006 Madrid, Spain.
authors.forename: Alma
authors.initials: A
authors.lastname: Viso
authors.affiliation: Instituto de Química Orgánica General, Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, E-28006 Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fernández de la Pradilla
authors.affiliation: Departamento de Química Física I.
authors.forename: Elena
authors.initials: E
authors.lastname: Junquera
authors.affiliation: Departamento de Química Física I.
authors.forename: Emilio
authors.initials: E
authors.lastname: Aicart
authors.affiliation: Departamento de Química Orgánica I.
authors.forename: Mar
authors.initials: M
authors.lastname: Martín-Fontecha
authors.affiliation: Departamento de Química Orgánica I.
authors.forename: Bellinda
authors.initials: B
authors.lastname: Benhamú
authors.affiliation: Departamento de Química Orgánica I.
authors.forename: María L
authors.initials: ML
authors.lastname: López-Rodríguez
authors.affiliation: Departamento de Química Orgánica I.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ortega-Gutiérrez
keywords: 5-HT1A receptor; G protein-coupled receptors (GPCRs); fluorescent ligands; probes; receptor visualization; serotonin (5-HT)