A Photohormone for Light-Dependent Control of PPARα in Live Cells.
J Med Chem
; 64(14): 10393-10402, 2021 07 22.
Article
em En
| MEDLINE
| ID: mdl-34213899
ABSTRACT
Photopharmacology enables the optical control of several biochemical processes using small-molecule photoswitches that exhibit different bioactivities in their cis- and trans-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 its trans-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
PPAR alfa
/
Hormônios
/
Luz
Limite:
Humans
Idioma:
En
Revista:
J Med Chem
Ano de publicação:
2021
Tipo de documento:
Article