Zhang Guo-Rong, Zhang Chi, Fu Ting, Tan Weihong, Wang Xue-Qiang
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, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
JACS Au. 2024 Aug 8;4(8):2907-2914. doi: 10.1021/jacsau.4c00260. eCollection 2024 Aug 26.
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.
靶向膜蛋白降解（TMPD）通过去除有害的膜锚定蛋白并促进对复杂生物途径的详细研究，具有巨大的治疗潜力。然而，现有的TMPD方法面临着诸如复杂的分子结构、可用性稀缺和构建要求繁琐等挑战。为了解决这些问题，本研究提出了一种高效的TMPD系统（TMPDS），该系统将优化的二价适体胶水与强大的蛋白质转运穿梭体相结合。利用这种方法，我们成功降解了CCRF-CEM细胞中高表达的蛋白酪氨酸激酶7以及MV-411细胞中低表达的PTK7。该系统代表了分子医学领域的重大进展，为靶向治疗干预和细胞机制探索提供了一条新途径。
