A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cells
Abstract Most luminescence-based technologies to determine the pharmacological properties of G Protein-Coupled Receptors (GPCRs) rely on the overexpression of genetically modified receptors. However, it is essential to develop approaches allowing the specific labelling of native receptors. Here we r...
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Nature Portfolio
2025-04-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01504-3 |
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| author | Xavier Gómez-Santacana Marin Boutonnet Carles Martínez-Juvés Marta Cimadevila Juanlo Catena Enora Moutin Thomas Roux Eric Trinquet Laurent Lamarque Julie Perroy Laurent Prézeau Jurriaan M. Zwier Jean-Philippe Pin Amadeu Llebaria |
| author_facet | Xavier Gómez-Santacana Marin Boutonnet Carles Martínez-Juvés Marta Cimadevila Juanlo Catena Enora Moutin Thomas Roux Eric Trinquet Laurent Lamarque Julie Perroy Laurent Prézeau Jurriaan M. Zwier Jean-Philippe Pin Amadeu Llebaria |
| author_sort | Xavier Gómez-Santacana |
| collection | DOAJ |
| description | Abstract Most luminescence-based technologies to determine the pharmacological properties of G Protein-Coupled Receptors (GPCRs) rely on the overexpression of genetically modified receptors. However, it is essential to develop approaches allowing the specific labelling of native receptors. Here we report an innovative approach based on the use of molecular modules to build fluorescent ligand-directed probes that can label aminergic GPCRs. Such probes are readily prepared with a click reaction between a ligand that may include nucleophilic groups and a fluorescent electrophilic linker. The rapidity of click reaction before receptor labelling prevents a side reaction between the nucleophilic ligand and the electrophile. This approach allowed us to label D1 receptor in transfected cells and native receptors in neural cell lines, leaving the receptor fully functional. This approach will pave the way to develop new reagents and assays with which to monitor endogenous GPCRs’ distribution, trafficking, activity or binding properties in their native environment. |
| format | Article |
| id | doaj-art-475b92cf00574b8199be82a06d9eb121 |
| institution | OA Journals |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-475b92cf00574b8199be82a06d9eb1212025-08-20T02:16:56ZengNature PortfolioCommunications Chemistry2399-36692025-04-018111210.1038/s42004-025-01504-3A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cellsXavier Gómez-Santacana0Marin Boutonnet1Carles Martínez-Juvés2Marta Cimadevila3Juanlo Catena4Enora Moutin5Thomas Roux6Eric Trinquet7Laurent Lamarque8Julie Perroy9Laurent Prézeau10Jurriaan M. Zwier11Jean-Philippe Pin12Amadeu Llebaria13Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS and INSERMInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS and INSERMMedicinal Chemistry & Synthesis, Institute for Advanced Chemistry of Catalonia (IQAC), Spanish Council for Scientific Research (CSIC)Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS and INSERMMedicinal Chemistry & Synthesis, Institute for Advanced Chemistry of Catalonia (IQAC), Spanish Council for Scientific Research (CSIC)Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS and INSERMRevvityRevvityRevvityInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS and INSERMInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS and INSERMRevvityInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS and INSERMMedicinal Chemistry & Synthesis, Institute for Advanced Chemistry of Catalonia (IQAC), Spanish Council for Scientific Research (CSIC)Abstract Most luminescence-based technologies to determine the pharmacological properties of G Protein-Coupled Receptors (GPCRs) rely on the overexpression of genetically modified receptors. However, it is essential to develop approaches allowing the specific labelling of native receptors. Here we report an innovative approach based on the use of molecular modules to build fluorescent ligand-directed probes that can label aminergic GPCRs. Such probes are readily prepared with a click reaction between a ligand that may include nucleophilic groups and a fluorescent electrophilic linker. The rapidity of click reaction before receptor labelling prevents a side reaction between the nucleophilic ligand and the electrophile. This approach allowed us to label D1 receptor in transfected cells and native receptors in neural cell lines, leaving the receptor fully functional. This approach will pave the way to develop new reagents and assays with which to monitor endogenous GPCRs’ distribution, trafficking, activity or binding properties in their native environment.https://doi.org/10.1038/s42004-025-01504-3 |
| spellingShingle | Xavier Gómez-Santacana Marin Boutonnet Carles Martínez-Juvés Marta Cimadevila Juanlo Catena Enora Moutin Thomas Roux Eric Trinquet Laurent Lamarque Julie Perroy Laurent Prézeau Jurriaan M. Zwier Jean-Philippe Pin Amadeu Llebaria A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cells Communications Chemistry |
| title | A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cells |
| title_full | A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cells |
| title_fullStr | A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cells |
| title_full_unstemmed | A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cells |
| title_short | A modular click ligand-directed approach to label endogenous dopamine D1 receptors in live cells |
| title_sort | modular click ligand directed approach to label endogenous dopamine d1 receptors in live cells |
| url | https://doi.org/10.1038/s42004-025-01504-3 |
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