A Photochromic Agonist for μ-Opioid Receptors

Authors

  • Matthias Schönberger,

    1. Department of Chemistry, Ludwig-Maximilians-University (LMU) Munich and Center of Integrated Protein Science, Butenandtstrasse 5–13, 81377 Munich (Germany)
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  • Prof. Dr. Dirk Trauner

    Corresponding author
    1. Department of Chemistry, Ludwig-Maximilians-University (LMU) Munich and Center of Integrated Protein Science, Butenandtstrasse 5–13, 81377 Munich (Germany)
    • Department of Chemistry, Ludwig-Maximilians-University (LMU) Munich and Center of Integrated Protein Science, Butenandtstrasse 5–13, 81377 Munich (Germany)===

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  • We thank Dr. Matthew Banghart (Harvard University) for assistance with the pharmacological testing of PF2 and for helpful discussions. M.S. is grateful to the Studienstiftung des Deutschen Volkes for a PhD fellowship. This work was supported by the European Science Foundation (ERC grant no. 268795 to D.T.).

Abstract

Opioid receptors (ORs) are widely distributed in the brain, the spinal cord, and the digestive tract and play an important role in nociception. All known ORs are G-protein-coupled receptors (GPCRs) of family A. Another well-known member of this family, rhodopsin, is activated by light through the cis/trans isomerization of a covalently bound chromophore, retinal. We now show how an OR can be combined with a synthetic azobenzene photoswitch to gain light sensitivity. Our work extends the reach of photopharmacology and outlines a general strategy for converting Family A GPCRs, which account for the majority of drug targets, into photoreceptors.

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