蛋白酶体
泛素
干扰素基因刺激剂
蛋白质降解
刺
细胞生物学
免疫疗法
癌症免疫疗法
化学
蛋白质水解
免疫系统
PD-L1
癌症研究
生物
生物化学
免疫学
先天免疫系统
受体
基因
酶
航空航天工程
工程类
作者
Wen Su,Mixiao Tan,Sheng Wang,Jie Zhang,Wenping Huang,Haohao Song,Xinye Wang,Haitao Ran,Yanfeng Gao,Guangjun Nie,Hai Wang
标识
DOI:10.1002/anie.202218128
摘要
Abstract Proteolysis targeting chimeras (PROTACs) technology is an emerging approach to degrade disease‐associated proteins. Here, we report carbon‐dot (CD)‐based PROTACs (CDTACs) that degrade membrane proteins via the ubiquitin‐proteasome system. CDTACs can bind to programmed cell death ligand 1 (PD‐L1), recruit cereblon (CRBN) to induce PD‐L1 ubiquitination, and degrade them with proteasomes. Fasting‐mimicking diet (FMD) is also used to enhance the cellular uptake and proteasome activity. More than 99 % or 90 % of PD‐L1 in CT26 or B16‐F10 tumor cells can be degraded by CDTACs, respectively. Furthermore, CDTACs can activate the stimulator of interferon genes (STING) pathway to trigger immune responses. Thus, CDTACs with FMD treatment effectively inhibit the growth of CT26 and B16‐F10 tumors. Compared with small‐molecule‐based PROTACs, CDTACs offer several advantages, such as efficient membrane protein degradation, targeted tumor accumulation, immune system activation, and in vivo detection.
科研通智能强力驱动
Strongly Powered by AbleSci AI