Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation

Jiwei Zheng1; Wanyi He1; Jing Li1; Xuejia Feng1; Yanyan Li1; Binghua Cheng1; Yimin Zhou1; Meiqing Li1; Ke Liu1; Ximing Shao1; Jianchao Zhang2; Hongchang Li1; Liang Chen1; Lijing Fang1

2022-11-23

10.1021/jacs.2c08367

Journal of the American Chemical Society   影响因子和分区

0002-7863

1520-5126

As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin-and lysosome-dependent manner. As demonstrated in the development of BMS-L1-RGD, which is an efficient programmed death-ligand 1 (PD-L1) degrader validated both in vitro and in vivo, the IFLD strategy expands the toolbox for regulation of secreted and membrane-associated proteins and thus has great potential to be applied in chemical biology and drug discovery.

SCI

英语

其他

[2021YFA0910000] ; [2020YFA0710802] ; [21977111] ; [22007096] ; [2019A1515012073] ; [2022A1515012030] ; [GJHZ20210705141407022] ; [JCYJ20210324120200001] ; [JCYJ20210324105007019]

Chemistry

Chemistry, Multidisciplinary

WOS:000889821600001

AMER CHEMICAL SOC

人工提交

在线出版

1.Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China
2.Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, China

Jiwei Zheng,Wanyi He,Jing Li,et al. Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation[J]. Journal of the American Chemical Society,2022.

Jiwei Zheng.,Wanyi He.,Jing Li.,Xuejia Feng.,Yanyan Li.,...&Lijing Fang.(2022).Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation.Journal of the American Chemical Society.

Jiwei Zheng,et al."Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation".Journal of the American Chemical Society (2022).