Synthesis of Photoswitchable Δ9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling
| Autor: | Dirk Trauner, Michael A. Imhof, James A. Frank, Christian P. Bold, Philipp Leippe, Jessica M. Grandner, Matthias Westphal, Amey Dhopeshwarkar, Michael A. Schafroth, Roman C. Sarott, Vsevolod Katritch, Erick M. Carreira, Ken Mackie |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Cannabinoid receptor
010405 organic chemistry Inward-rectifier potassium ion channel Central nervous system General Chemistry 010402 general chemistry Inhibitory postsynaptic potential 01 natural sciences Biochemistry Catalysis 0104 chemical sciences 3. Good health Adenylyl cyclase Electrophysiology chemistry.chemical_compound Colloid and Surface Chemistry Förster resonance energy transfer medicine.anatomical_structure chemistry mental disorders medicine Biophysics Receptor |
| Zdroj: | Journal of the American Chemical Society. 139:18206-18212 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | The cannabinoid receptor 1 (CB1) is an inhibitory G protein-coupled receptor abundantly expressed in the central nervous system. It has rich pharmacology and largely accounts for the recreational use of cannabis. We describe efficient asymmetric syntheses of four photoswitchable Δ9-tetrahydrocannabinol derivatives (azo-THCs) from a central building block 3-Br-THC. Using electrophysiology and a FRET-based cAMP assay, two compounds are identified as potent CB1 agonists that change their effect upon illumination. As such, azo-THCs enable CB1-mediated optical control of inwardly rectifying potassium channels, as well as adenylyl cyclase. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|