An Aptamer Glue Enables Hyperefficient Targeted Membrane Protein Degradation.

JACS Au

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.

Published: August 2024

AI Article Synopsis

  • Targeted membrane protein degradation (TMPD) is a promising therapy for eliminating harmful membrane proteins and studying biological pathways.
  • Current TMPD methods have limitations, including complex designs and availability issues.
  • This study introduces an efficient TMPD system that combines an improved aptamer glue with a strong protein transport shuttle, successfully degrading specific proteins in different cell lines, indicating progress in molecular medicine.

Article Abstract

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350568PMC
http://dx.doi.org/10.1021/jacsau.4c00260DOI Listing

Publication Analysis

Top Keywords

aptamer glue
8
targeted membrane
8
membrane protein
8
protein degradation
8
glue enables
4
enables hyperefficient
4
hyperefficient targeted
4
protein
4
degradation targeted
4
degradation tmpd
4

Similar Publications

Efficient and Rapid Enrichment of Extracellular Vesicles Using DNA Nanotechnology-Enabled Synthetic Nano-Glue.

Anal Chem

January 2025

The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China.

Swift and efficient enrichment and isolation of extracellular vesicles (EVs) are crucial for enhancing precise disease diagnostics and therapeutic strategies, as well as elucidating the complex biological roles of EVs. Conventional methods of isolating EVs are often marred by lengthy and laborious processes. In this study, we introduce an innovative approach to enrich and isolate EVs by leveraging the capabilities of DNA nanotechnology.

View Article and Find Full Text PDF

Targeted protein degradation (TPD) has emerged as a prominent and vital strategy for therapeutic intervention of cancers and other diseases. One such approach involves the exploration of proteolysis targeting chimeras (PROTACs) for the selective elimination of disease-causing proteins through the innate ubiquitin-proteasome pathway. Due to the unprecedented achievements of various PROTAC molecules in clinical trials, researchers have moved towards other physiological protein degradation approaches for the targeted degradation of abnormal proteins, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs), molecular glue degraders, and other derivatives for their precise mode of action.

View Article and Find Full Text PDF

An Aptamer Glue Enables Hyperefficient Targeted Membrane Protein Degradation.

JACS Au

August 2024

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.

Article Synopsis
  • Targeted membrane protein degradation (TMPD) is a promising therapy for eliminating harmful membrane proteins and studying biological pathways.
  • Current TMPD methods have limitations, including complex designs and availability issues.
  • This study introduces an efficient TMPD system that combines an improved aptamer glue with a strong protein transport shuttle, successfully degrading specific proteins in different cell lines, indicating progress in molecular medicine.
View Article and Find Full Text PDF

Chemical Tailoring of Aptamer Glues with Significantly Enhanced Recognition Ability for Targeted Membrane Protein Degradation.

ACS Nano

August 2023

Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.

Cell membrane proteins play a crucial role in the development of early cancer diagnosis strategies and precision medicine techniques. However, the application of aptamers in cell membrane protein-based biomedical research is limited by their inherent drawbacks, such as sensitivity to the recognition environment and susceptibility to enzymatic degradation, which leads to the loss of recognition ability. To address these challenges, this study presents a subzero-temperature-enabled molecule stacking strategy for the on-demand tailoring of aptamer glues for the precision recognition and efficient degradation of membrane protein.

View Article and Find Full Text PDF

Unlocking the potential of PROTACs: A comprehensive review of protein degradation strategies in disease therapy.

Bioorg Chem

October 2023

Department of Pharmacognosy, Goa College of Pharmacy, Panaji, Goa University, Goa 403001, India. Electronic address:

The technology known asPROTACs (PROteolysisTArgeting Chimeras) is a method of protein degradation. Utilising bifunctional small molecules, the ubiquitin-proteosome system (UPS) is used to induce the ubiquitination and degradation of target proteins. In addition to being novel chemical knockdown agents for biological studies that are catalytic, reversible, and rapid, PROTACs used in the treatment for disorders like cancer, immunological disorders, viral diseases, and neurological disorders.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!