TY - JOUR
T1 - Development of Fluorescent Probes that Target Serotonin 5-HT2B Receptors
AU - Azuaje, Jhonny
AU - López, Paula
AU - Iglesias, Alba
AU - De La Fuente, Rocío A.
AU - Pérez-Rubio, José M.
AU - García, Diego
AU - Stȩpniewski, Tomasz Maciej
AU - García-Mera, Xerardo
AU - Brea, José M.
AU - Selent, Jana
AU - Pérez, Dolores
AU - Castro, Marián
AU - Loza, María I.
AU - Sotelo, Eddy
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Some 5-HT2B fluorescent probes were obtained by tagging 1-(2,5-dimethoxy-4-iodophenyl)-propan-2-amine (DOI) with a subset of fluorescent amines. Some of the resulting fluorescent ligands showed excellent affinity and selectivity profiles at the 5-HT2B receptors (e.g. 12b), while retain the agonistic functional behaviour of the model ligand (DOI). The study highlighted the most salient features of the structure-activity relationship in this series and these were substantiated by a molecular modelling study based on a receptor-driven docking model constructed on the basis of the crystal structure of the human 5-HT2B receptor. One of the fluorescent ligands developed in this work, compound 12i, specifically labelled CHO-K1 cells expressing 5-HT2B receptors and not parental CHO-K1 cells in a concentration-dependent manner. 12i enables imaging and quantification of specific 5-HT2B receptor labelling in live cells by automated fluorescence microscopy as well as quantification by measurements of fluorescence intensity using a fluorescence plate reader.
AB - Some 5-HT2B fluorescent probes were obtained by tagging 1-(2,5-dimethoxy-4-iodophenyl)-propan-2-amine (DOI) with a subset of fluorescent amines. Some of the resulting fluorescent ligands showed excellent affinity and selectivity profiles at the 5-HT2B receptors (e.g. 12b), while retain the agonistic functional behaviour of the model ligand (DOI). The study highlighted the most salient features of the structure-activity relationship in this series and these were substantiated by a molecular modelling study based on a receptor-driven docking model constructed on the basis of the crystal structure of the human 5-HT2B receptor. One of the fluorescent ligands developed in this work, compound 12i, specifically labelled CHO-K1 cells expressing 5-HT2B receptors and not parental CHO-K1 cells in a concentration-dependent manner. 12i enables imaging and quantification of specific 5-HT2B receptor labelling in live cells by automated fluorescence microscopy as well as quantification by measurements of fluorescence intensity using a fluorescence plate reader.
UR - http://www.scopus.com/inward/record.url?scp=85029125651&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-11370-2
DO - 10.1038/s41598-017-11370-2
M3 - Article
AN - SCOPUS:85029125651
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 10765
ER -