靶向多次跨膜蛋白的抗体药物研究进展  

Research Progress of Antibody Drugs Targeting Multipass Membrane Proteins

作　　者：丁燕超 曾子颜 郑培源 霍苑桐 杜娟娟 DING Yanchao;ZENG Ziyan;ZHENG Peiyuan;HUO Yuantong;DU Juanjuan(School of Pharmaceutical Sciences,MOE Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical Biology,Tsinghua University,Beijing 100084,China)

机构地区：[1]清华大学药学院生命有机磷化学教育部重点实验室,北京100084

出　　处：《药学进展》2024年第1期41-56,共16页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金(No.8237130404)。

摘　　要：多次跨膜蛋白作为连接细胞膜内外环境的重要渠道,参与多种信号的传导,调控细胞对外界刺激的响应。许多人类疾病都与多次跨膜蛋白功能异常密切相关,使它们成为理想的药物作用靶点。相较于以小分子和多肽为主导的现有治疗方式,基于抗体的药物具有特异性强等优势,为调控多次跨膜蛋白的功能提供了新的路径。然而,针对多次跨膜蛋白进行抗体药物研发也面临诸多挑战,其结构的复杂性产生了例如表位可及性、蛋白表达困难和蛋白动态构象等独特障碍,需要创新性策略来推动相应的抗体药物研发。对多次跨膜蛋白因复杂结构为抗体药物开发所带来的挑战进行探讨,以及对近年来为克服这些障碍所发展的新方法进行介绍,并且系统性总结目前在研的针对多次跨膜蛋白的抗体类药物。相信随着该领域的发展,从靶向多次跨膜蛋白的抗体药物研究中获得的见解不仅对改进治疗干预措施,而且对推进更广泛的药物研究创新具有重大意义。Multipass membrane proteins serve as crucial channels connecting the intracellular and extracellular environments of cells,transmitting various signals and regulating cellular responses to external stimuli.Many human diseases are closely associated with abnormalities in the function of multipass membrane proteins,making them ideal targets for drug intervention.In comparison to existing treatment approaches dominated by small molecules and peptides,antibody-based drugs offer advantages such as high specificity,providing a new avenue for regulating the function of multipass membrane proteins.However,the development of antibody drugs targeting multipass membrane proteins faces numerous challenges.The complexity of their structure presents unique obstacles,including epitope accessibility,difficulties in protein expression,and dynamic protein conformations.Innovative strategies are needed to drive corresponding antibody drug development.This discussion explores the challenges posed by the complex structures of multipass membrane proteins for antibody drug development and introduces new approaches developed in recent years to overcome these obstacles.The review systematically summarizes current antibody drug research targeting multipass membrane proteins.As this field progresses,insights gained from antibody drug discovery targeting multipass membrane proteins not only contribute to improving therapeutic interventions but also hold significant value for advancing broader drug discovery innovations.

关 键 词：抗体药物 G蛋白偶联受体 离子通道 转运蛋白 多次跨膜蛋白 

分 类 号：R969.1[医药卫生—药理学]