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Delivering on Cell-Selective Protein Degradation Using Chemically Tailored PROTACs
Rui Yao1,2, Tianli Luo1,2, Ming Wang1,2
1Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
Chembiochem : a European Journal of Chemical Biology
|July 26, 2023
Summary
Proteolysis-Targeting Chimeras (PROTACs) enable targeted protein degradation. Newer Pro-PROTACs offer controlled degradation via external stimuli and advanced delivery systems for enhanced in vivo applications.
Area of Science:
- Chemical Biology
- Molecular Biology
- Drug Discovery
Background:
- PROTACs are chemical tools that harness the ubiquitin-proteasome system for targeted protein degradation.
- Current PROTAC applications face challenges in cell selectivity and in vivo efficacy.
- Controlled protein degradation is crucial for advanced therapeutic strategies.
Purpose of the Study:
- To review recent advancements in Pro-PROTACs for controlled protein degradation.
- To explore chemical strategies for regulating PROTAC-E3 ligase and PROTAC-target interactions.
- To summarize nanoparticle-based delivery systems for in vivo PROTAC applications.
Main Methods:
- Review of recent scientific literature on Pro-PROTACs and delivery systems.
- Analysis of chemical strategies for spatial and temporal control of protein degradation.
- Synthesis of findings on biodegradable nanoparticles for targeted in vivo delivery.
Main Results:
- Pro-PROTACs demonstrate controlled degradation in response to stimuli.
- Chemical strategies enable precise regulation of PROTAC activity.
- Biodegradable nanoparticles show promise for efficient and selective in vivo PROTAC delivery.
Conclusions:
- Pro-PROTACs offer enhanced control over protein degradation.
- Advanced delivery systems are key for effective in vivo applications.
- Future designs focus on multifunctional PROTACs and cell-selective delivery.
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