Development of Fluorescent Probes that Target Serotonin 5-HT2B Receptors

Jhonny Azuaje, Paula López, Alba Iglesias, Rocío A. De La Fuente, José M. Pérez-Rubio, Diego García, Tomasz Maciej Stȩpniewski, Xerardo García-Mera, José M. Brea, Jana Selent, Dolores Pérez, Marián Castro, María I. Loza, Eddy Sotelo

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number10765
Number of pages16
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017
Externally publishedYes

Cite this