靶向蛋白翻译后修饰的药物化学生物学研究  

Chemical biology research on targeting protein post-translational modifications

作　　者：陶泓儒 张元元 陈文韬 陈子墨 徐颖 李昊 周璐[5] 韩记昌 邓贤明[7] 李林 陈国强 罗成 Hongru Tao;Yuanyuan Zhang;Wentao Chen;Zimo Chen;Ying Xu;Hao Li;Lu Zhou;Jichang Han;Xianming Deng;Lin Li;Guoqiang Chen;Cheng Luo(School of Drug Science and Technology,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China;Center for Chemical Biology,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;Department of Pathophysiology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Neurosurgery,Children’s Hospital of Fudan University,Shanghai 201210,China;Department of Medicinal Chemistry,School of Pharmacy,Fudan University,Shanghai 201203,China;Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,Shanghai 200031,China;School of Life Sciences,National and Local Joint Engineering Laboratory of Natural Products-Derived Targeted Drugs,Xiamen University,Xiamen 361102,China;Institute of Aging and Tissue Repair,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)

机构地区：[1]国科大杭州高等研究院,药物科学与技术学院,杭州310024 [2]中国科学院上海药物研究所,化学生物学中心,上海201203 [3]上海交通大学医学院,病理生理学系,上海200025 [4]复旦大学附属儿科医院神经外科,上海201210 [5]复旦大学药学院药物化学系,上海201203 [6]中国科学院分子细胞科学卓越创新中心,上海200031 [7]厦门大学生命科学学院,天然产物源靶向药物国家地方联合工程实验室,厦门361102 [8]上海交通大学医学院附属仁济医院,衰老与组织修复研究院,上海200127

出　　处：《中国科学:化学》2025年第4期777-784,共8页SCIENTIA SINICA Chimica

基　　金：国家自然科学基金(编号:92253303)资助项目。

摘　　要：蛋白质作为生命活动的核心执行者,其功能多样性主要源于翻译后修饰(PTMs)的动态变化.PTMs如甲基化、磷酸化和SUMO化等,是分子间相互作用、信号传导和网络调控的关键靶点,几乎涉及细胞生长、存活和免疫应答等所有生命活动.这些修饰的异常会导致蛋白质功能失调,进而引发多种疾病.随着多组学技术的发展,与重大疾病相关的蛋白质修饰及其调控酶不断被发现,这不仅拓展了PTMs在重大疾病中的功能解析,也推动了靶向PTMs的小分子药物开发.研究PTMs机制并鉴定相关靶标,可加速基础研究向药物开发转化,为重大疾病的诊疗提供理论基础.本综述旨在:(1)总结PTMs及其调控酶在肿瘤生长、转移和免疫逃逸中的功能和分子机制;(2)概括PTMs位点功能预测的前沿技术和新方法;(3)综述靶向PTMs机制的先导化合物发现策略和研究进展.本综述将为靶向PTMs开发抗肿瘤药物提供新的干预靶点、创新策略、研究技术和经验参考.Proteins,as the core executors of biological activities,exhibit diverse functions primarily due to the dynamic changes in post-translational modifications(PTMs),such as methylation,phosphorylation,and SUMOylation.These PTMs are critical targets for molecular interactions,signaling,and network regulation,and are involved in nearly all biological activities,including cell growth,survival,and immune response.Aberrant PTMs can lead to protein dysfunction and subsequent diseases.The development of multi-omics technologies has led to the continuous identification of disease-related PTMs and regulatory enzymes,expanding the understanding of PTMs in major diseases and promoting the development of small-molecule drugs targeting PTMs.Investigating PTM mechanisms and identifying relevant targets can accelerate the translation of basic research into drug development,providing a theoretical basis for the diagnosis and treatment of major diseases.This review aims to:(1)summarize the functions and mechanisms of PTMs and regulatory enzymes in tumor growth,metastasis,and immune evasion;(2)outline cuttingedge technologies and new methods for predicting PTM site functions;(3)review strategies and progress in discovering lead compounds targeting PTM mechanisms.Ultimately,it provides new intervention targets,innovative strategies,research technologies,and references for the development of anti-tumor drugs targeting PTMs.

关 键 词：肿瘤 蛋白翻译后修饰 功能 干预靶点 药物研发 

分 类 号：R730.5[医药卫生—肿瘤]