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/PMC11350568 | PMC |
http://dx.doi.org/10.1021/jacsau.4c00260 | DOI Listing |
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 PDFPharmacol Ther
November 2024
Drug Discovery Unit (DDU), Centre for Biomaterials, Cellular and Molecular Theranostics (CBCMT), Vellore Institute of Technology (VIT), Vellore 632014, India. Electronic address:
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 PDFJACS 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.
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 PDFBioorg 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 PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!