DataVXACS NanoPaper
journal article·2023-08-08

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

Guo-Rong Zhang, Weihong Tan, Xue-Qiang Wang

ACS Nano· Volume 17· Issue 15
Publisher page
Source abstract

Abstract

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. Mechanistic studies revealed that nucleic acid molecule stacking occurred during the freezing and melting processes, facilitating a rapid click reaction by bringing two reactive groups together. In vitro investigations demonstrated that the strategy confers aptamer glues with significantly enhanced specific recognition ability and binding affinity, allowing the distinction of a targeted cell line from a nontargeted cell line. Moreover, the engineered aptamer glue exhibited impressive targeted cell membrane protein degradation ability; around 74% of the c-Met protein was degraded in 24 h. These findings hold great potential for advancing cancer diagnosis and targeted therapy through the development of more stable and reliable aptamer probes.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · Protein Degradation and Inhibitors

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

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

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

Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

Key Laboratory of Organosilicon Chemistry and Material Technology of Ministry of Education, Hangzhou Normal University, Hangzhou 311121, China

Funding

National Key Research and Development Program of China · Science and Technology Program of Hunan Province · Distinguished Young Scholar Foundation of Hunan Province · Ministry of Education Key Laboratory of Organosilicon Chemistry and Material Technology, Hangzhou Normal University

References (24)

Show source-provided references
1. 10.1038/s41467-019-10920-810.1038/s41467-019-10920-8 ↗
2. 10.1038/nmeth.289510.1038/nmeth.2895 ↗
3. 10.1007/s00232-011-9381-710.1007/s00232-011-9381-7 ↗
4. 10.1053/j.gastro.2022.03.05610.1053/j.gastro.2022.03.056 ↗
5. 10.1186/s13045-019-0833-310.1186/s13045-019-0833-3 ↗
6. 10.1038/s41571-021-00470-810.1038/s41571-021-00470-8 ↗
7. 10.1016/j.trecan.2023.01.00310.1016/j.trecan.2023.01.003 ↗
8. 10.1021/jacs.1c0957410.1021/jacs.1c09574 ↗
9. 10.1016/j.addr.2018.08.00610.1016/j.addr.2018.08.006 ↗
10. 10.1038/s41570-017-007610.1038/s41570-017-0076 ↗
11. 10.1038/346818a010.1038/346818a0 ↗
12. 10.1126/science.220012110.1126/science.2200121 ↗
13. 10.1038/nrd.2016.19910.1038/nrd.2016.199 ↗
14. 10.1016/j.biotechadv.2021.10790210.1016/j.biotechadv.2021.107902 ↗
15. 10.1002/anie.20221810610.1002/anie.202218106 ↗
16. 10.31635/ccschem.021.20210133710.31635/ccschem.021.202101337 ↗
17. 10.1038/s41570-019-0079-110.1038/s41570-019-0079-1 ↗
18. 10.1021/acs.bioconjchem.7b0063310.1021/acs.bioconjchem.7b00633 ↗
19. 10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-510.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5 ↗
20. The Nobel Prize in Chemistry 2022. NobelPrize.org. Nobel Prize Outreach AB 2023. Mon. 24 Jul 2023; https://www.nobelprize.org/prizes/chemistry/2022/summary/.
21. 10.1021/ja044996f10.1021/ja044996f ↗
22. 10.1021/jacs.9b0446110.1021/jacs.9b04461 ↗
23. 10.1002/anie.20210950010.1002/anie.202109500 ↗
24. 10.1093/nsr/nwac10710.1093/nsr/nwac107 ↗