In the cell membrane, Transient receptor potential melastatin 8 (TRPM8) channels act as receptors for cold and cooling agents like menthol, enabling humans to sense cold. Since this protein influences pain perception and plays a vital role in numerous diseases, they are promising targets for developing new drugs.
In recent years, there have been several studies on TRPM8 ion channels to get insights into their complex functions and develop innovative therapeutic approaches. To further decipher the role of TRPM8, researchers at Ludwig-Maximilians-Universitat have developed a photoswitchable TRPM8 channel activator based on the natural cooling agent menthol.
The team developed a molecule called azo-menthol, which precisely controls TRPM8 channels using light. Azo-menthol can be switched ON and OFF with the spatiotemporal precision of light.
Photoswitching is generally achieved by incorporating a photoswitchable azobenzene moiety, a chemical structure that changes its configuration when exposed to UV or blue light. The recent advances in photopharmacology, using light to control drugs, allowed researchers to control protein function simply by switching light.
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Lead author says, “With azo-menthol, it’s possible for the first time to specifically activate TRPM8 channels using UV light and deactivate them again with blue light – and to do so in a way that’s spatiotemporally precise and reversible.“
“Such photopharmacological approaches could help, for example, avoid systemic side effects such as arise during conventional chemotherapy. Accordingly, the progress being made in this area opens up exciting new prospects for the development of novel therapies that could be more precise in their action and gentler in their effects,” adds Mederos y Schnitzler.
Journal Reference
- Becker, J., Ellerkmann, C. S., Schmelzer, H., Hermann, C., Lützel, K., Gudermann, T., Konrad, D. B., Trauner, D., & Storch, U. Optical Control of TRPM8 Channels with Photoswitchable Menthol. Angewandte Chemie International Edition. DOI: 10.1002/anie.202416549
