Development of molecular probes for the human 5-HT(6) receptor.
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.
Vázquez-Villa
Henar
H
Departamento de Química Orgánica I, Facultad de Ciencias Quı´micas, Universidad Complutense deMadrid, E-28040 Madrid, Spain.
González-Vera
Juan A
JA
Benhamú
Bellinda
B
Viso
Alma
A
Fernández de la Pradilla
Roberto
R
Junquera
Elena
E
Aicart
Emilio
E
López-Rodríguez
María L
ML
Ortega-Gutiérrez
Silvia
S
D001667:Binding, Competitive; D001710:Biotin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D019921:Biotinylation; D002460:Cell Line; D003619:Dansyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism
C553290:5-(dimethylamino)-N-(3-(4-(4-(((5-(dimethylamino)-1-naphthyl)sulfonyl)amino)butyl)piperazin-1-yl)-4-methoxyphenyl)naphthalene-1-sulfonamide; D003619:Dansyl Compounds; D005456:Fluorescent Dyes; D008024:Ligands; D015335:Molecular Probes; C553289:N-(6-(4-(5-(((5-chloro-3-methyl-1-benzothien-2-yl)sulfonyl)amino)-2-methoxyphenyl)piperazin-1-yl)hexyl)-5-(-2-oxohexahydro-1H-thieno(3,4-d)imidazol-4-yl)pentanamide; D010879:Piperazines; D011985:Receptors, Serotonin; D013449:Sulfonamides; C097216:serotonin 6 receptor; D001710:Biotin