自然杂志 >

2023 , Vol. 45 >Issue 6: 434 - 442

DOI: https://doi.org/10.3969/j.issn.0253-9608.2023.06.008

科技进展

膜蛋白靶向降解技术研究进展

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  • ①贵州大学 药学院，贵阳 550025；②深圳湾实验室，广东 深圳 518000；③贵州大学 绿色农药与农业生物工程国家重点实验室培育基地，贵阳 550025

收稿日期: 2022-12-30

  网络出版日期: 2023-12-21

基金资助

国家自然科学基金青年基金(22007022)、贵州省科技拔尖人才项目(黔教技[2022]075)、贵州省教育厅重点项目(QjhKYZi[2021]041)

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Research progress in targeted degradation of membrane proteins

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  • ① School of pharmaceutical sciences, Guizhou University, Guiyang 550025, China; ② Shenzhen Bay Laboratory, Shenzhen 518000, Guangdong Province, China; ③ State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Guizhou University, Guiyang 550025, China

Received date: 2022-12-30

  Online published: 2023-12-21

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摘要

膜蛋白是细胞间相互作用的主要参与者，在信号传导、分化增殖、应激响应等生命过程中均扮演着重要的角色。传统小分子抑制剂与抗体分别通过抑制和阻断膜蛋白与其配体之间的相互作用来发挥作用，但往往存在抑制不彻底或诱发耐药性的问题。新兴的蛋白质靶向降解技术为药物发现提供了全新思路，通过在溶酶体或蛋白酶体中特异性降解目的蛋白，使其彻底丧失蛋白质功能，极大地拓展了成药范围。文章简要讨论了近年来膜蛋白靶向降解技术的研究进展，并展望这些技术在临床治疗中的广阔应用前景。

关键词： 膜蛋白; 靶向降解; 蛋白质功能

本文引用格式

赵俗, 张衡, 李焱, 王贞超 . 膜蛋白靶向降解技术研究进展[J]. 自然杂志, 2023 , 45(6) : 434 -442 . DOI: 10.3969/j.issn.0253-9608.2023.06.008

Abstract

Membrane proteins are the major participants in cell-cell interactions, and play important roles in many essential cellular processes, such as signal transduction, differentiation, proliferation, and stress response. Traditional small molecule inhibitors and antibodies can play a role by inhibiting and blocking the interactions between membrane proteins and their ligands, but there are often problems of incomplete inhibition or induction of drug resistance. The emerging protein targeted degradation technologies provide a new area for drug discovery. The function of protein is completely lost by specifically degrading in lysosome or proteasome, which expands significantly the drugable scope. This review briefly discusses research progress about targeted membrane protein degradation technologies and presents the promising application of these technologies in clinic.

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