LAUSR

Photopharmacology aims at the optical control of protein activity using synthetic photoswitches. This approach has been recently expanded to nuclear hormone receptors with the introduction of 'photohormones' for retinoic acid receptor, farnesoid X receptor and estrogen receptor. Herein, we report the development and profiling of photoswitchable agonists for peroxisome proliferator-activated receptor  (PPAR. Based on known PPAR ligands (MDG548, GW1929 and Rosiglitazone) we have designed and synthesized azobenzene derivatives, termed AzoGW1929 and AzoRosi, which were confirmed to be active in cell-based assays. Subsequent computer-aided optimization of AzoRosi resulted in the photohormone AzoRosi-4 which bound and activated PPAR preferentially in its light-activated cis-configuration.