Bifunctional Peptide Nanofibrils for Targeted Protein Degradation

Zongtao Lin, Benjamin A. Garcia, Dongwen Lv

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 languageEnglish (US)
Article numbere202316581
JournalAngewandte Chemie - International Edition
Volume63
Issue number3
DOIs
StatePublished - Jan 15 2024

Keywords

  • Cancer
  • Nanofibril
  • PROTAC
  • Self-Assembly
  • Targeted Protein Degradation

ASJC Scopus subject areas

  • General Chemistry
  • Catalysis

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