Direkt zum Inhalt

Becker, Jasmin ; Ellerkmann, Clara S. ; Schmelzer, Hannah ; Hermann, Christian ; Lützel, Kyra ; Gudermann, Thomas ; Konrad, David B. ; Trauner, Dirk ; Storch, Ursula ; Mederos y Schnitzler, Michael

Optical Control of TRPM8 Channels with Photoswitchable Menthol

Becker, Jasmin, Ellerkmann, Clara S., Schmelzer, Hannah, Hermann, Christian, Lützel, Kyra, Gudermann, Thomas, Konrad, David B., Trauner, Dirk, Storch, Ursula und Mederos y Schnitzler, Michael (2024) Optical Control of TRPM8 Channels with Photoswitchable Menthol. Angewandte Chemie International Edition.

Veröffentlichungsdatum dieses Volltextes: 07 Jan 2025 10:32
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.74555


Zusammenfassung

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 ...

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.



Beteiligte Einrichtungen


Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftAngewandte Chemie International Edition
Verlag:Wiley
Datum11 Dezember 2024
InstitutionenChemie und Pharmazie > Institut für Pharmazie
Identifikationsnummer
WertTyp
10.1002/anie.202416549DOI
Stichwörter / Keywordsphotopharmacology · ion channels · TRPM8 · photoswitchable menthol · current kinetics ms an
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenZum Teil
URN der UB Regensburgurn:nbn:de:bvb:355-epub-745551
Dokumenten-ID74555

Bibliographische Daten exportieren

Nur für Besitzer und Autoren: Kontrollseite des Eintrags

nach oben