A Photohormone for Light-Dependent Control of PPARα in Live Cells

Sabine Willems, Johannes Morstein, Konstantin Hinnah, Dirk Trauner, Daniel Merk

Research output: Contribution to journalArticlepeer-review

Abstract

Photopharmacology enables the optical control of several biochemical processes using small-molecule photoswitches that exhibit different bioactivities in theircis- andtrans-conformations. Such tool compounds allow for high spatiotemporal control of biological signaling, and the approach also holds promise for the development of drug molecules that can be locally activated to reduce target-mediated adverse effects. Herein, we present the expansion of the photopharmacological arsenal to two new members of the peroxisome proliferator-activated receptor (PPAR) family, PPARα and PPARδ. We have developed a set of highly potent PPARα and PPARδ targeting photohormones derived from the weak pan-PPAR agonist GL479 that can be deactivated by light. The photohormone 6 selectively activated PPARα in itstrans-conformation with high selectivity over the related PPAR subtypes and was used in live cells to switch PPARα activity on and off in a light- and time-dependent fashion.

Original languageEnglish (US)
Pages (from-to)10393-10402
Number of pages10
JournalJournal of Medicinal Chemistry
Volume64
Issue number14
DOIs
StatePublished - Jul 22 2021

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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