Abstract
Proteolysis targeting chimera (PROTAC) is a state-of-the-art technology for ablating undruggable targets. A PROTAC degrader achieves targeted protein degradation (TPD) through the simultaneous binding of a protein of interest (POI) and an E3 ligase to form a ternary complex. A nanofibril-based PROTAC strategy to form a polynary (E3)m : PROTAC : (POI)n complex has not been reported in the TPD field up to this point. A recent innovation shows that a POI ligand and E3 ligase ligand don't have to be within a fused degrader molecule. Instead, they can be recruited to cellular proximity by a self-assembly-driving peptide and click chemistry. The resulting nanofibrils can recruit multiple POI and E3 ligase molecules to form a polynary complex as a degradation center. The so-called Nano-PROTAC provides a novel approach for TPD in cancer therapy.
Original language | English |
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Article number | e202316581 |
Journal | Angewandte Chemie - International Edition |
Volume | 63 |
Issue number | 3 |
DOIs | |
State | Published - Jan 15 2024 |
Keywords
- Cancer
- Nanofibril
- PROTAC
- Self-Assembly
- Targeted Protein Degradation