Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers

Photopharmacology relies on ligands that change their pharmacodynamics upon photoisomerization. Many of these ligands are azobenzenes that are thermodynamically more stable in their elongated trans‐configuration. Often, they are biologically active in this form and lose activity upon irradiation and...

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Bibliographic Details
Published in:Angewandte Chemie 2019-10, Vol.131 (43), p.15567-15574
Main Authors: Trads, Julie B., Hüll, Katharina, Matsuura, Bryan S., Laprell, Laura, Fehrentz, Timm, Görldt, Nicole, Kozek, Krystian A., Weaver, C. David, Klöcker, Nikolaj, Barber, David M., Trauner, Dirk
Format: Article
Language:English
Subjects:
Biological activity
Channels
Chemistry
Diazocine
GIRK-Kanäle
Inversion
Irradiation
Kaliumkanäle
Ligands
Pharmacodynamics
Pharmacology
Photochromism
Photopharmakologie
Photoschaltbare Moleküle
Potassium
Potassium channels
Potassium channels (inwardly-rectifying)
Potassium channels (voltage-gated)
Radiation
Switches
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Summary:Photopharmacology relies on ligands that change their pharmacodynamics upon photoisomerization. Many of these ligands are azobenzenes that are thermodynamically more stable in their elongated trans‐configuration. Often, they are biologically active in this form and lose activity upon irradiation and photoisomerization to their cis‐isomer. Recently, cyclic azobenzenes, so‐called diazocines, have emerged, which are thermodynamically more stable in their bent cis‐form. Incorporation of these switches into a variety of photopharmaceuticals could convert dark‐active ligands into dark‐inactive ligands, which is preferred in most biological applications. This “pharmacological sign‐inversion” is demonstrated for a photochromic blocker of voltage‐gated potassium channels, termed CAL, and a photochromic opener of G protein‐coupled inwardly rectifying potassium (GIRK) channels, termed CLOGO. Der Tausch von Standard‐Azobenzolen gegen Diazocine ermöglicht die „Vorzeichenumkehr” von Photopharmazeutika, wie anhand eines photoschaltbaren Kaliumkanalblockers und eines Kanalöffners demonstriert wird.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201905790