Becker, Jasmin and Ellerkmann, Clara S. and Schmelzer, Hannah and Hermann, Christian and Luetzel, Kyra and Gudermann, Thomas and Konrad, David B. and Trauner, Dirk and Storch, Ursula and Schnitzler, Michael (2025) Optical Control of TRPM8 Channels with Photoswitchable Menthol. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 64 (5). ISSN , 1521-3773
Full text not available from this repository. (Request a copy)Abstract
Transient receptor potential melastatin 8 (TRPM8) channels are well known as sensors for cold temperatures and cooling agents such as menthol and icilin and these channels are tightly regulated by the membrane lipid phosphoinositol-4,5-bisphosphate (PIP2). Since TRPM8 channels emerged as promising drug targets for treating pain, itching, obesity, cancer, dry eye disease, and inflammation, we aimed at developing a high-precision TRPM8 channel activator, to achieve spatiotemporal control of TRPM8 activity with light. In this study, we designed, synthesized and characterized the first photoswitchable TRPM8 activator azo-menthol (AzoM). AzoM enables optical control of endogenously and heterologously expressed TRPM8 channels with UV and blue light which is demonstrated by performing patch-clamp experiments. Moreover, AzoM facilitates the reliable determination of activation, inactivation, and deactivation kinetics thereby providing further insights into the channel gating. Using AzoM, the specific roles of individual amino acids for AzoM or PIP2 binding and for sensitization by PIP2 can be elucidated. Altogether, AzoM represents as a high-precision pharmaceutical tool for reversible control of TRPM8 channel function that enhances our biophysical understanding of TRPM8 channels and holds the potential to support the development of novel pharmaceuticals.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLD RECEPTOR; ACTIVATION; REVEALS; MECHANISM; SENSATION; ALCOHOLS; BINDING; PROTEIN; ICILIN; RISK; photopharmacology; ion channels; TRPM8; photoswitchable menthol; current kinetics |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Group Clinical Pharmacy (Dr. Dorn) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2026 10:57 |
| Last Modified: | 24 Mar 2026 10:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64938 |
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