title: Bivalent Ligands for the Serotonin 5-HT3 Receptor.
abstract: The serotonin 5-HT3 receptor is a ligand-gated ion channel, which by virtue of its pentameric architecture, can be considered to be an intriguing example of intrinsically multivalent biological receptors. This paper describes a general design approach to the study of multivalency in this multimeric ion channel. Bivalent ligands for 5-HT3 receptor have been designed by linking an arylpiperazine moiety to probes showing different functional features. Both homobivalent and heterobivalent ligands have shown 5-HT3 receptor affinity in the nanomolar range, providing evidence for the viability of our design approach. Moreover, the high affinity shown by homobivalent ligands suggests that bivalency is a promising approach in 5-HT3 receptor modulation and provides the rational basis for applying the concepts of multivalency to the study of 5-HT3 receptor function.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università di Siena , Via A. Moro, 53100 Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cappelli
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università di Siena , Via A. Moro, 53100 Siena, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Manini
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università di Siena , Via A. Moro, 53100 Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Paolino
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università di Siena , Via A. Moro, 53100 Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallelli
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università di Siena , Via A. Moro, 53100 Siena, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Anzini
authors.affiliation: Rottapharm Madaus , Via Valosa di Sopra 9, 20052 Monza, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mennuni
authors.affiliation: Dipartimento di Chimica, Università di Modena e Reggio Emilia , Via Campi 183, 41100 Modena, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Del Cadia
authors.affiliation: Dipartimento di Chimica, Università di Modena e Reggio Emilia , Via Campi 183, 41100 Modena, Italy ; Centro S3, CNR-Istituto di Nanoscienze , Via Campi 213A, 41125 Modena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Rienzo
authors.affiliation: Dipartimento di Chimica, Università di Modena e Reggio Emilia , Via Campi 183, 41100 Modena, Italy.
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Menziani
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico and European Research Centre for Drug Discovery and Development, Università di Siena , Via A. Moro, 53100 Siena, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vomero
keywords: 5-HT3; Serotonin receptors; bivalent ligands; molecular modeling; multivalency