Development of molecular probes for the human 5-HT(6) receptor.

ABSTRACT

In this work we report the synthesis of a set of labeled ligands targeting the human 5-HT(6) receptor (h5-HT(6)R). Among the synthesized compounds, fluorescent probe 10 (K(i) = 175 nM and Φ(f) = 0.21) and biotinylated derivative 15 (K(i) = 90 nM) deserve special attention because they enable direct observation of the h5-HT(6)R in cells. Thus, they represent the first molecular probes for 5-HT(6)R visualization. These results are the starting point for introducing a variety of tags in these or other 5-HT(6)R ligand scaffolds aimed at the development of optimized probes with tailored profiles in terms of fluorescence, affinity, or selectivity.