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Sci Rep. 2017 Sep 7;7(1):10765. doi: 10.1038/s41598-017-11370-2.

Development of Fluorescent Probes that Target Serotonin 5-HT2B Receptors.

Author information

1
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782, Santiago de Compostela, Spain.
2
Departamento de Química Orgánica, Facultad de Farmacia, Universidade de Santiago de Compostela, E-15782, Santiago de Compostela, Spain.
3
Instituto de Farmacia Industrial (IFI), Universidade de Santiago de Compostela, E-15782, Santiago de Compostela, Spain.
4
Centro Singular de Investigación en Medicina Molecular e Enfermidades Crónicas (CIMUS), Universidade de Santiago de Compostela, E-15782, Santiago de Compostela, Spain.
5
PharmacoInformatics Group, Research Program on Biomedical Informatics (GRIB) PRBB, Barcelona, 08003, Spain.
6
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, 02-093, Warsaw, Poland.
7
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782, Santiago de Compostela, Spain. e.sotelo@usc.es.
8
Departamento de Química Orgánica, Facultad de Farmacia, Universidade de Santiago de Compostela, E-15782, Santiago de Compostela, Spain. e.sotelo@usc.es.
9
Instituto de Farmacia Industrial (IFI), Universidade de Santiago de Compostela, E-15782, Santiago de Compostela, Spain. e.sotelo@usc.es.

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.

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