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Optical Control of Dopamine Receptors Using a Photoswitchable Tethered Inverse Agonist

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† Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, United States
‡ Department of Chemistry and Center for Integrated Protein Science, Ludwig-Maximilians-Universität, Butenandtstraße 5-13, Munich 81377, Germany
§ Departments of Psychiatry and Pharmacology, Columbia University, New York, New York 10027, United States
∥ Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York 10032, United States
⊥ Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, United States
# Bioscience Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
∇ Department of Chemistry, New York University, New York, New York 10003, United States
*[email protected]
*[email protected]
Cite this: J. Am. Chem. Soc. 2017, 139, 51, 18522–18535
Publication Date (Web):November 22, 2017
https://doi.org/10.1021/jacs.7b07659
Copyright © 2017 American Chemical Society
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    Abstract

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    Family A G protein-coupled receptors (GPCRs) control diverse biological processes and are of great clinical relevance. Their archetype rhodopsin becomes naturally light sensitive by binding covalently to the photoswitchable tethered ligand (PTL) retinal. Other GPCRs, however, neither bind covalently to ligands nor are light sensitive. We sought to impart the logic of rhodopsin to light-insensitive Family A GPCRs in order to enable their remote control in a receptor-specific, cell-type-specific, and spatiotemporally precise manner. Dopamine receptors (DARs) are of particular interest for their roles in motor coordination, appetitive, and aversive behavior, as well as neuropsychiatric disorders such as Parkinson’s disease, schizophrenia, mood disorders, and addiction. Using an azobenzene derivative of the well-known DAR ligand 2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT), we were able to rapidly, reversibly, and selectively block dopamine D1 and D2 receptors (D1R and D2R) when the PTL was conjugated to an engineered cysteine near the dopamine binding site. Depending on the site of tethering, the ligand behaved as either a photoswitchable tethered neutral antagonist or inverse agonist. Our results indicate that DARs can be chemically engineered for selective remote control by light and provide a template for precision control of Family A GPCRs.

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    9. Katharina Hüll, Johannes Morstein, Dirk Trauner. In Vivo Photopharmacology. Chemical Reviews 2018, 118 (21) , 10710-10747. https://doi.org/10.1021/acs.chemrev.8b00037
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    12. Wan-Chen Lin, Richard H. Kramer. Light-Switchable Ion Channels and Receptors for Optogenetic Interrogation of Neuronal Signaling. Bioconjugate Chemistry 2018, 29 (4) , 861-869. https://doi.org/10.1021/acs.bioconjchem.7b00803
    13. Ehud Y. Isacoff, Andreas Reiner. Optogenetics. 2023, 179-191. https://doi.org/10.1016/B978-0-12-821618-7.00150-4
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    16. Kasey S. Girven, Leandra Mangieri, Michael R. Bruchas. Emerging approaches for decoding neuropeptide transmission. Trends in Neurosciences 2022, 76 https://doi.org/10.1016/j.tins.2022.09.005
    17. Carlo Matera, Pablo Calvé, Verònica Casadó-Anguera, Rosalba Sortino, Alexandre M. J. Gomila, Estefanía Moreno, Thomas Gener, Cristina Delgado-Sallent, Pau Nebot, Davide Costazza, Sara Conde-Berriozabal, Mercè Masana, Jordi Hernando, Vicent Casadó, M. Victoria Puig, Pau Gorostiza. Reversible Photocontrol of Dopaminergic Transmission in Wild-Type Animals. International Journal of Molecular Sciences 2022, 23 (17) , 10114. https://doi.org/10.3390/ijms231710114
    18. Michael H. Berry, Amy Holt, Johannes Broichhagen, Prashant Donthamsetti, John G. Flannery, Ehud Y. Isacoff. Photopharmacology for vision restoration. Current Opinion in Pharmacology 2022, 65 , 102259. https://doi.org/10.1016/j.coph.2022.102259
    19. Silvia Panarello, Xavier Rovira, Amadeu Llebaria, Xavier Gómez‐Santacana. Photopharmacology of G ‐Protein‐Coupled Receptors. 2022, 921-944. https://doi.org/10.1002/9783527827626.ch37
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