PUBLICATION
Light-induced protein degradation with photo-caged PROTACs
- Authors
- Xue, G., Wang, K., Zhou, D., Zhong, H., Pan, Z.
- ID
- ZDB-PUB-191001-9
- Date
- 2019
- Source
- Journal of the American Chemical Society 141(46): 18370-18374 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Cycle Proteins/chemistry
- Cell Line
- Humans
- Light*
- Proteolysis/drug effects*
- Proteolysis/radiation effects*
- Small Molecule Libraries/chemistry
- Small Molecule Libraries/pharmacology*
- Transcription Factors/chemistry
- Zebrafish/embryology
- Zebrafish/physiology
- Zebrafish Proteins/chemistry
- PubMed
- 31566962 Full text @ J. Am. Chem. Soc.
Citation
Xue, G., Wang, K., Zhou, D., Zhong, H., Pan, Z. (2019) Light-induced protein degradation with photo-caged PROTACs. Journal of the American Chemical Society. 141(46):18370-18374.
Abstract
Induction of protein degradation is emerging as a powerful strategy to modulate protein functions and alter cellular signaling pathways. Proteolysis-targeting chimeras (PROTACs) have been used to degrade a range of diverse proteins in vitro and in vivo. Here we present a type of photo-caged PROTACs (pc-PROTACs) to induce degradation activity with light. Photo-removable blocking groups were added to a degrader of Brd4, and the resulting molecule pc-PROTAC1 showed potent degradation activity in live cells only after light irradiation. Furthermore, this molecule efficiently degraded Brd4 and induced expected phenotypic changes in zebrafish. Additionally, this approach was successfully applied to construct pc-PROTAC3 of BTK. Thus a general strategy to induce protein degradation with light was established to augment the chemists' toolbox to study disease-relevant protein targets.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping