ACHEMS 2019
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SPLTRAK Abstract Submission
Optopharmacology Of Odorants: Photoactivatable Ligands For Chemosensory Research
Kirill Ukhanov1,2, Sangram Gore4, Cyril Herbivo4, Naeem Asad4, Yuriy Bobkov2,3, Jeffrey R Martens1,2, Timothy R Dore4
1University of Florida, Gainesville, FL, United States
2New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
3New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
4New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
5University of Florida, St.Augustine, FL, United States
6University of Florida, Gainesville, FL, United States
7New York University Abu Dhabi, Abu Dhabi, United Arab Emirates

The chemosensory system of any animal relies on a vast array of detectors tuned to distinct chemical cues. Odorant receptors and the ion channels of the TRP family are all uniquely expressed in a species-specific manner. Great effort has been made to characterize the molecular and pharmacological identity of these proteins. Nevertheless, most of the natural ligands are highly hydrophobic molecules preventing controlled delivery. We sought to develop photoprotected, biologically inactive odorants that could be delivered to the target receptor or ion channel and effectively activated by a short light pulse. Eugenol, benzaldehyde, 2-phenyl ethylamine, butanethiol, and ethanethiol were modified by covalently attaching the photoremovable protecting group (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ). CyHQ derivatives were characterized in vitro and shown to release the active odorant upon illumination with 365-nm light. We characterized their bioactivity by measuring the electroolfactogram (EOG) from mouse olfactory epithelium. Activation was dependent on light pulse duration and intensity. The kinetics of the light-activated response was compared with a the EOG evoked by a pulse of vaporized amyl acetate. In addition, we tested the applicability of the approach to activate TRPA1 and TRPV1 ion channels heterologously expressed in HEK293 cells. The photorelease of eugenol and both thiol compounds perfusing the HEK293-TRPA1 cells robustly activated inward ion currents within milliseconds of the light pulse. Photoactivation of TRPA1 channels was far superior to activation by conventional bath application of the ligands. Illumination with 405 nm light was also sufficient to activate TRPV1 channels. We conclude that photoprotected odorants can be successfully implemented in chemosensory research.