Photohormones Enable Optical Control of the Peroxisome Proliferator-Activated Receptor γ (PPARγ).
J Med Chem
; 63(19): 10908-10920, 2020 10 08.
Article
in En
| MEDLINE
| ID: mdl-32886507
ABSTRACT
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 the retinoic acid receptor, farnesoid X receptor, and estrogen receptor. Herein, we report the development and profiling of photoswitchable agonists for peroxisome proliferator-activated receptor γ (PPARγ). Based on known PPARγ 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 PPARγ preferentially in its light-activated cis-configuration.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
PPAR gamma
/
Light
Limits:
Animals
/
Humans
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2020
Document type:
Article
Affiliation country:
United States