Lysosome Targeting Chimaeras for Glut1-Facilitated Targeted Protein Degradation.

Autor:	Luo J; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China.; University of Chinese Academy of Sciences, Beijing 100049, China., Gao Q; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China., Tan K; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China., Zhang S; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China., Shi W; Department of Chemical Biology, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China., Luo L; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China., Li Z; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China., Khedr GE; Department of Analysis and Evaluation, Egyptian Petroleum Research Institute, Cairo 11727, Egypt., Chen J; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China., Xu Y; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China., Luo M; Polariton Life, Suzhou 215004, Jiangsu, China., Xing Q; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China., Geng J; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2024 Jul 03; Vol. 146 (26), pp. 17728-17737. Date of Electronic Publication: 2024 Jun 20.
DOI:	10.1021/jacs.4c02463
Abstrakt:	Targeted protein degradation technology holds great potential in biomedicine, particularly in treating tumors and other protein-related diseases. Research on intracellular protein degradation using molecular glues and PROTAC technology is leading, while research on the degradation of membrane proteins and extracellular proteins through the lysosomal pathway is still in the preclinical stage. The scarcity of useful targets is an immense limitation to technological advancement, making it essential to explore novel, potentially effective approaches for targeted lysosomal degradation. Here, we employed the glucose transporter Glut1 as an innovative lysosome-targeting receptor and devised the Glut1-Facilitated Lysosomal Degradation (GFLD) strategy. We synthesized potential Glut1 ligands via reversible addition-fragmentation chain transfer (RAFT) polymerization and acquired antibody-glycooligomer conjugates through bioorthogonal reactions as lysosome-targeting protein degradation molecules, utilized in the management of PD-L1 high-expressing triple-negative breast cancer. The glucose transporter Glut1 as a lysosome-targeting receptor exhibits potential for the advancement of a broader array of medications in the future.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu