Izquierdo Serra, MercèBautista-Barrufet, AntoniTrapero, AnaGarrido-Charles, AidaDíaz-Tahoces, AriadnaCamarero, NuriaPittolo, SilviaValbuena, SergioPérez-Jiménez, AriadnaGay, MarinaGarcía-Moll, AlejandroLlebaria, AmadeuGorostiza, Pau2024-01-292024-01-292016Izquierdo-Serra M, Bautista-Barrufet A, Trapero A, Garrido-Charles A, Díaz-Tahoces A, Camarero N, et al. Optical control of endogenous receptors and cellular excitability using targeted covalent photoswitches. Nat Commun. 2016 Jul 20;7(1):12221. DOI: 10.1038/ncomms122212041-1723http://hdl.handle.net/10230/58845Light-regulated drugs allow remotely photoswitching biological activity and enable plausible therapies based on small molecules. However, only freely diffusible photochromic ligands have been shown to work directly in endogenous receptors and methods for covalent attachment depend on genetic manipulation. Here we introduce a chemical strategy to covalently conjugate and photoswitch the activity of endogenous proteins and demonstrate its application to the kainate receptor channel GluK1. The approach is based on photoswitchable ligands containing a short-lived, highly reactive anchoring group that is targeted at the protein of interest by ligand affinity. These targeted covalent photoswitches (TCPs) constitute a new class of light-regulated drugs and act as prosthetic molecules that photocontrol the activity of GluK1-expressing neurons, and restore photoresponses in degenerated retina. The modularity of TCPs enables the application to different ligands and opens the way to new therapeutic opportunities.application/pdfengThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.MedicamentsMedicaments biològicsNeuronesVisióinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/ncomms12221info:eu-repo/semantics/openAccess