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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Julie B. Trads, Ludwig-Maximilians-University München
  • ,
  • Katharina Hüll, Ludwig-Maximilians-University München, New York University
  • ,
  • Bryan S. Matsuura, Ludwig-Maximilians-University München, New York University
  • ,
  • Laura Laprell, Ludwig-Maximilians-University München
  • ,
  • Timm Fehrentz, Heinrich Heine University Düsseldorf
  • ,
  • Nicole Görldt, Heinrich Heine University Düsseldorf
  • ,
  • Krystian A. Kozek, Vanderbilt Institute for Global Health (VIGH)
  • ,
  • C. David Weaver, Vanderbilt Institute for Global Health (VIGH)
  • ,
  • Nikolaj Klöcker, Heinrich Heine University Düsseldorf
  • ,
  • David M. Barber, Ludwig-Maximilians-University München
  • ,
  • Dirk Trauner, Ludwig-Maximilians-University München, New York University

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
JournalAngewandte Chemie - International Edition
Volume58
Issue43
Pages (from-to)15421-15428
Number of pages8
ISSN1433-7851
DOIs
Publication statusPublished - 2019

    Research areas

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

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