Lysosome Targeting Chimaeras for Glut1-Facilitated Targeted Protein Degradation

Luo, Jinyan1,2; Gao, Quan1; Tan, Kui1; Zhang, Shiling1; Shi, Weiwei3; Luo, Lei1; Li, Zhiying1; Khedr, Ghada E.4; Chen, Jie1; Xu, Youwei1; Luo, Ming5; Xing, Qi1; Geng, Jin1

2024-06-20

10.1021/jacs.4c02463

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   影响因子和分区

0002-7863

1520-5126

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.

SCI ; EI

英语

其他

Commonwealth Scientific and Industrial Research Organisation[22071263] ; National Natural Science Foundation of China[2020A1515010994] ; Natural Science Foundation of Guangdong Province, China[2019QN01Y127] ; Guangdong Province Zhujiang Talents Program[172644KYSB20200048]

Chemistry

Chemistry, Multidisciplinary

WOS:001252182000001

AMER CHEMICAL SOC

20242616349466

Biosynthesis ; Chelation ; Proteins

Biotechnology:461.8 ; Biochemistry:801.2 ; Chemical Reactions:802.2 ; Organic Compounds:804.1

Web of Science

1.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen 518055, Guangdong, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Southern Univ Sci & Technol, Dept Chem Biol, Shenzhen 518055, Guangdong, Peoples R China
4.Egyptian Petr Res Inst, Dept Anal & Evaluat, Cairo 11727, Egypt
5.Polariton Life, Suzhou 215004, Jiangsu, Peoples R China

Luo, Jinyan,Gao, Quan,Tan, Kui,et al. Lysosome Targeting Chimaeras for Glut1-Facilitated Targeted Protein Degradation[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2024,146(26):17728-17737.

Luo, Jinyan.,Gao, Quan.,Tan, Kui.,Zhang, Shiling.,Shi, Weiwei.,...&Geng, Jin.(2024).Lysosome Targeting Chimaeras for Glut1-Facilitated Targeted Protein Degradation.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,146(26),17728-17737.

Luo, Jinyan,et al."Lysosome Targeting Chimaeras for Glut1-Facilitated Targeted Protein Degradation".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 146.26(2024):17728-17737.