Dosing PPARγ Activation With Light Using Fast Relaxing Photoswitches

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • Loris Knümann - (Author)
  • Alba Rodriguez‐Paniagua - (Author)
  • Martin Reynders - , Chair of Organic Chemistry II (Author)
  • Silke Duensing‐Kropp - (Author)
  • Oliver Thorn‐Seshold - , Chair of Organic Chemistry II (Author)
  • Vasily Morozov - (Author)
  • Julian A. Marschner - (Author)
  • Daniel Merk - (Author)

Abstract

The transcription factor PPARγ regulates glucose and lipid homeostasis, and its activation, e.g., with glitazones, has antidiabetic, insulin-sensitizing activity, but also adverse effects which possibly arise from overstimulation. Here we developed a novel high-precision tool to enable light-dosed PPARγ activation. Structure-guided incorporation of a photoswitchable diazene motif into a PPARγ ligand and molecular fine-tuning provided potent, light-activated PPARγ agonists with millisecond to multiple-hour half-lives, suitable for biological research applications. Phenotypic effects of light-dosed PPARγ activation in an in vitro model of adipogenesis suggested time-dependent importance of the receptor in adipocyte development and illustrated the unprecedented precision of controlling PPARγ activity with light-activated chemical tools.

Details

Original languageEnglish
Article numbere7525141
JournalAngewandte Chemie International Edition
Volume65
Issue number40
Publication statusPublished - 28 Sept 2026
Peer-reviewedYes

External IDs

Scopus 105047755047

Keywords