Molecule of the Month
March 2010
Enlightened Ion Channels

Ligand-gated ion channels (LGICs), such as the serotonin (5-HT) type 3 receptor (5-HT3R), are responsible for rapid transmission of nerve impulses at synapses. The 5-HT3R is an attractive therapeutic target, however, its transmembrane nature hampers efforts to obtain high resolution structures. Using high-affinity biophysical probes to investigate the structure and function of LGICs is a complementary strategy.
The picture shows a stick model of BFL-GR, a fluorescent ligand, which binds with high affinity to the human 5 HT3R (in ribbon diagram) and can visualise 5-HT3Rs expressed in mammalian cells (photograph).

This work was carried out in the groups of Prof. Martin Lochner and Dr. Sarah Lummis (Cambridge).

References:

  • S. K. Vernekar, H. Y. Hallaq, G. Clarkson, A. J. Thompson, L. Silvestri, S. C. R. Lummis, M. Lochner;
    "Toward Biophysical Probes for the 5-HT3 Receptor: Structure-Activity Relationship Study of Granisetron Derivatives"
    J. Med. Chem., 53, 23242328, (2010); doi:10.1021/jm901827x.