An Aptamer Glue Enables Hyperefficient Targeted Membrane Protein Degradation.
Guo-Rong ZhangChi ZhangTing FuWeihong TanXue-Qiang WangPublished in: JACS Au (2024)
Targeted membrane protein degradation (TMPD) offers significant therapeutic potential by enabling the removal of harmful membrane-anchored proteins and facilitating detailed studies of complex biological pathways. However, existing TMPD methodologies face challenges such as complex molecular architectures, scarce availability, and cumbersome construction requirements. To address these issues, this study presents a highly efficient TMPD system (TMPDS) that integrates an optimized bivalent aptamer glue with a potent protein transport shuttle. Utilizing this approach, we successfully degraded both the highly expressed protein tyrosine kinase 7 in CCRF-CEM cells and the poorly expressed PTK7 in MV-411 cells. This system represents significant advancement in the field of molecular medicine, offering a new avenue for targeted therapeutic interventions and the exploration of cellular mechanisms.
Keyphrases
- tyrosine kinase
- highly efficient
- induced apoptosis
- cell cycle arrest
- cancer therapy
- epidermal growth factor receptor
- protein protein
- sensitive detection
- drug delivery
- binding protein
- single molecule
- cell death
- signaling pathway
- small molecule
- oxidative stress
- cell proliferation
- quantum dots
- label free
- magnetic nanoparticles