Fluorescent ligands for dopamine D2/D3 receptors

Abstract Fluorescent ligands are versatile tools for the study of G protein-coupled receptors. Depending on the fluorophore, they can be used for a range of different applications, including fluorescence microscopy and bioluminescence or fluorescence resonance energy transfer (BRET or FRET) assays....

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Autores principales:	Anni Allikalt, Nirupam Purkayastha, Khajidmaa Flad, Maximilian F. Schmidt, Alina Tabor, Peter Gmeiner, Harald Hübner, Dorothee Weikert
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/917ec5091e204abdb7245329c218d9c8
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spelling	oai:doaj.org-article:917ec5091e204abdb7245329c218d9c82021-12-02T12:42:18ZFluorescent ligands for dopamine D2/D3 receptors10.1038/s41598-020-78827-92045-2322https://doaj.org/article/917ec5091e204abdb7245329c218d9c82020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78827-9https://doaj.org/toc/2045-2322Abstract Fluorescent ligands are versatile tools for the study of G protein-coupled receptors. Depending on the fluorophore, they can be used for a range of different applications, including fluorescence microscopy and bioluminescence or fluorescence resonance energy transfer (BRET or FRET) assays. Starting from phenylpiperazines and indanylamines, privileged scaffolds for dopamine D2-like receptors, we developed dansyl-labeled fluorescent ligands that are well accommodated in the binding pockets of D2 and D3 receptors. These receptors are the target proteins for the therapy for several neurologic and psychiatric disorders, including Parkinson’s disease and schizophrenia. The dansyl-labeled ligands exhibit binding affinities up to 0.44 nM and 0.29 nM at D2R and D3R, respectively. When the dansyl label was exchanged for sterically more demanding xanthene or cyanine dyes, fluorescent ligands 10a-c retained excellent binding properties and, as expected from their indanylamine pharmacophore, acted as agonists at D2R. While the Cy3B-labeled ligand 10b was used to visualize D2R and D3R on the surface of living cells by total internal reflection microscopy, ligand 10a comprising a rhodamine label showed excellent properties in a NanoBRET binding assay at D3R.Anni AllikaltNirupam PurkayasthaKhajidmaa FladMaximilian F. SchmidtAlina TaborPeter GmeinerHarald HübnerDorothee WeikertNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anni Allikalt Nirupam Purkayastha Khajidmaa Flad Maximilian F. Schmidt Alina Tabor Peter Gmeiner Harald Hübner Dorothee Weikert Fluorescent ligands for dopamine D2/D3 receptors
description	Abstract Fluorescent ligands are versatile tools for the study of G protein-coupled receptors. Depending on the fluorophore, they can be used for a range of different applications, including fluorescence microscopy and bioluminescence or fluorescence resonance energy transfer (BRET or FRET) assays. Starting from phenylpiperazines and indanylamines, privileged scaffolds for dopamine D2-like receptors, we developed dansyl-labeled fluorescent ligands that are well accommodated in the binding pockets of D2 and D3 receptors. These receptors are the target proteins for the therapy for several neurologic and psychiatric disorders, including Parkinson’s disease and schizophrenia. The dansyl-labeled ligands exhibit binding affinities up to 0.44 nM and 0.29 nM at D2R and D3R, respectively. When the dansyl label was exchanged for sterically more demanding xanthene or cyanine dyes, fluorescent ligands 10a-c retained excellent binding properties and, as expected from their indanylamine pharmacophore, acted as agonists at D2R. While the Cy3B-labeled ligand 10b was used to visualize D2R and D3R on the surface of living cells by total internal reflection microscopy, ligand 10a comprising a rhodamine label showed excellent properties in a NanoBRET binding assay at D3R.
format	article
author	Anni Allikalt Nirupam Purkayastha Khajidmaa Flad Maximilian F. Schmidt Alina Tabor Peter Gmeiner Harald Hübner Dorothee Weikert
author_facet	Anni Allikalt Nirupam Purkayastha Khajidmaa Flad Maximilian F. Schmidt Alina Tabor Peter Gmeiner Harald Hübner Dorothee Weikert
author_sort	Anni Allikalt
title	Fluorescent ligands for dopamine D2/D3 receptors
title_short	Fluorescent ligands for dopamine D2/D3 receptors
title_full	Fluorescent ligands for dopamine D2/D3 receptors
title_fullStr	Fluorescent ligands for dopamine D2/D3 receptors
title_full_unstemmed	Fluorescent ligands for dopamine D2/D3 receptors
title_sort	fluorescent ligands for dopamine d2/d3 receptors
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/917ec5091e204abdb7245329c218d9c8
work_keys_str_mv	AT anniallikalt fluorescentligandsfordopamined2d3receptors AT nirupampurkayastha fluorescentligandsfordopamined2d3receptors AT khajidmaaflad fluorescentligandsfordopamined2d3receptors AT maximilianfschmidt fluorescentligandsfordopamined2d3receptors AT alinatabor fluorescentligandsfordopamined2d3receptors AT petergmeiner fluorescentligandsfordopamined2d3receptors AT haraldhubner fluorescentligandsfordopamined2d3receptors AT dorotheeweikert fluorescentligandsfordopamined2d3receptors
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Fluorescent ligands for dopamine D2/D3 receptors

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