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

Julie B. Trads, Katharina Hüll, Bryan S. Matsuura, Laura Laprell, Timm Fehrentz, Nicole Görldt, Krystian A. Kozek, C. David Weaver, Nikolaj Klöcker, David M. Barber, Dirk Trauner

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)15421-15428
Number of pages8
JournalAngewandte Chemie - International Edition
Volume58
Issue number43
DOIs
StatePublished - Oct 21 2019

Fingerprint

Potassium Channel Blockers
Azobenzene
Potassium
Ligands
Photoisomerization
G Protein-Coupled Inwardly-Rectifying Potassium Channels
Pharmacodynamics
Voltage-Gated Potassium Channels
GTP-Binding Proteins
Isomers
Switches
Irradiation
Proteins
azobenzene
Electric potential

Keywords

  • diazocines
  • GIRK channels
  • photopharmacology
  • photoswitchable molecules
  • potassium channels

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

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

In: Angewandte Chemie - International Edition, Vol. 58, No. 43, 21.10.2019, p. 15421-15428.

Research output: Contribution to journalArticle

Trads, JB, Hüll, K, Matsuura, BS, Laprell, L, Fehrentz, T, Görldt, N, Kozek, KA, Weaver, CD, Klöcker, N, Barber, DM & Trauner, D 2019, 'Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers', Angewandte Chemie - International Edition, vol. 58, no. 43, pp. 15421-15428. https://doi.org/10.1002/anie.201905790
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. / Sign Inversion in Photopharmacology : Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers. In: Angewandte Chemie - International Edition. 2019 ; Vol. 58, No. 43. pp. 15421-15428.
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