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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.

SUBMITTER: Cappelli A

PROVIDER: S-EPMC4018136 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Bivalent Ligands for the Serotonin 5-HT3 Receptor.

Cappelli Andrea A Manini Monica M Paolino Marco M Gallelli Andrea A Anzini Maurizio M Mennuni Laura L Del Cadia Marta M De Rienzo Francesca F Menziani M Cristina MC Vomero Salvatore S

ACS medicinal chemistry letters 20110509 8

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 ha ...[more]

PMID: 24900351

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