Development of a targeted BioPROTAC degrader selective for misfolded SOD1 | Nature Communications
Conventional PROTACs have limited capacity for misfolded proteins. Here, authors develop a BioPROTAC containing an scFv specifically targeting misfolded SOD1, fused to an E3 ligase, and demonstrate a strategy for reducing misfolded SOD1 accumulation.
Introduction Targeted protein degradation (TPD) is an emerging therapeutic strategy that leverages endogenous protein quality control systems to selectively degrade disease-associated proteins. TPD utilises bifunctional molecules in an induced proximity approach1, which brings together target proteins and key players in the ubiquitin proteasome (UPS) or the lysosomal autophagy degradation pathways, to degrade target proteins2. The induced proximity strategy has the potential to revolutionise the treatment of neurodegenerative diseases characterised by the accumulation of misfolded or toxic…
saved by
related reading
- Lysosome-targeting chimaeras for degradation of extracellular proteins | Naturenature.com
- PDB101: Molecule of the Month: PROTACs and Molecular Glue Degraderspdb101.rcsb.org
- Protein degradation reaches further outnature.com
- Lysosome-targeting chimeras evolve | Nature Chemical Biologynature.com
- One-shot design of functional protein binders with BindCraftnature.com
- Technologies to measure and modulate protein subcellular localizationnature.com
- TGP, an extremely stable, non-aggregating fluorescent protein created by structure-guided surface engineeringpmc.ncbi.nlm.nih.gov
- Engineering Plastic-Degrading Enzymes and PCSK9 Binders with Protein AI Toolsblog.latch.bio
- AlphaProteo generates novel proteins for biology and health researchdeepmind.google
- Topos Bio - Redefining Druggable Spacetoposbio.ai
- AlphaFolddeepmind.google
- Interspecies Differences in Proteome Turnover Kinetics Are Correlated With Life Spans and Energetic Demandsncbi.nlm.nih.gov