Development of visible-light-activatable photocaged PROTACs.
Eur J Med Chem
; 265: 116062, 2024 Feb 05.
Article
em En
| MEDLINE
| ID: mdl-38128235
ABSTRACT
Photocaged proteolysis-targeting chimeras (PROTACs), which employ light as a stimulus to control protein degradation, have recently garnered considerable attention as both powerful chemical tools and a promising therapeutic strategy. However, the poor penetration depth of traditionally used ultraviolet light and the deficiency of alternative caging positions have restricted their applications in biological systems. By installing a diverse array of photocaged groups, with excitation wavelengths ranging from 365 nm to 405 nm, onto different positions of cereblon (CRBN) and Von Hippel-Lindau (VHL)-recruiting Brd4 degraders, we conducted the first comprehensive study on visible-light-activatable photocaged PROTACs to the best of our knowledge. We found the A2, A4 and B3 positions to be most effective at regulating the activity of the degraders, and to provide the resulting molecules (9-12 and 17) as potent visible-light-controlled degraders in live cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Proteína Supressora de Tumor Von Hippel-Lindau
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article