title: Photoswitchable fatty acids enable optical control of TRPV1.
abstract: Fatty acids (FAs) are not only essential components of cellular energy storage and structure, but play crucial roles in signalling. Here we present a toolkit of photoswitchable FA analogues (FAAzos) that incorporate an azobenzene photoswitch along the FA chain. By modifying the FAAzos to resemble capsaicin, we prepare a series of photolipids targeting the Vanilloid Receptor 1 (TRPV1), a non-selective cation channel known for its role in nociception. Several azo-capsaicin derivatives (AzCAs) emerge as photoswitchable agonists of TRPV1 that are relatively inactive in the dark and become active on irradiation with ultraviolet-A light. This effect can be rapidly reversed by irradiation with blue light and permits the robust optical control of dorsal root ganglion neurons and C-fibre nociceptors with precision timing and kinetics not available with any other technique. More generally, we expect that photolipids will find many applications in controlling biological pathways that rely on protein-lipid interactions.
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstrasse 5-13, Munich 81377, Germany.
authors.forename: James Allen
authors.initials: JA
authors.lastname: Frank
authors.affiliation: Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Moroni
authors.affiliation: 1] Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany [2] Department of Anesthesiology, Campus Charité Mitte und Virchow Klinikum, Charité Universitätsmedizin Berlin, Augustburgerplatz 1, Berlin 13353, Germany.
authors.forename: Rabih
authors.initials: R
authors.lastname: Moshourab
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstrasse 5-13, Munich 81377, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Sumser
authors.affiliation: Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin 13125, Germany.
authors.forename: Gary R
authors.identifier: 0000000228906352
authors.initials: GR
authors.lastname: Lewin
authors.affiliation: Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich, Butenandtstrasse 5-13, Munich 81377, Germany.
authors.forename: Dirk
authors.identifier: 0000000267826056
authors.initials: D
authors.lastname: Trauner
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D001920:Bradykinin; D002211:Capsaicin / Q000031:analogs & derivatives; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives; D050356:Lipid Metabolism; D051379:Mice; D055668:Photochemical Processes; D010777:Photochemistry / Q000379:methods*; D012701:Serotonin; D050916:TRPV Cation Channels / Q000819:agonists*
chemical_list: D001391:Azo Compounds; D005227:Fatty Acids; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C493921:TRPV1 protein, mouse; C012647:QX-314; D012701:Serotonin; D008012:Lidocaine; D002211:Capsaicin; D001920:Bradykinin