Dosing PPARγ Activation With Light Using Fast Relaxing Photoswitches

Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung

Beitragende

  • Loris Knümann - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Alba Rodriguez‐Paniagua - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Martin Reynders - , Professur für Organische Chemie (II) (OC2) (Autor:in)
  • Silke Duensing‐Kropp - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Oliver Thorn‐Seshold - , Professur für Organische Chemie (II) (OC2) (Autor:in)
  • Vasily Morozov - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Julian A. Marschner - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)
  • Daniel Merk - , Ludwig-Maximilians-Universität München (LMU) (Autor:in)

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

OriginalspracheEnglisch
Aufsatznummere7525141
FachzeitschriftAngewandte Chemie International Edition
Jahrgang65
Ausgabenummer40
PublikationsstatusVeröffentlicht - 28 Sept. 2026
Peer-Review-StatusJa

Externe IDs

Scopus 105047755047

Schlagworte

ASJC Scopus Sachgebiete

  • Allgemeine Chemie - transcription factor, adipogenesis, lipid metabolism, peroxisome proliferator-activated receptor gamma, photoswitch

Schlagwörter

  • transcription factor, adipogenesis, lipid metabolism, peroxisome proliferator-activated receptor gamma, photoswitch