Hao Yuechen, Zhang Baoshuang, Chen Ruibing
School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China.
School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Tianjin 300072, China.
J Pharm Biomed Anal. 2025 Aug 15;261:116829. doi: 10.1016/j.jpba.2025.116829. Epub 2025 Mar 19.
The advent of targeted protein degradation technologies, particularly Proteolysis-Targeting Chimeras (PROTACs), enable the selective elimination of target proteins and open up new avenues for the treatment of various diseases. This review delves into the pivotal role of mass spectrometry (MS) in the advancement of PROTACs. MS-based methodologies serve as invaluable tools for identifying PROTAC targets, validating their efficacy, and elucidating ubiquitination sites and protein degradation dynamics. These insights profoundly enrich our comprehension of the mechanisms of action and facilitate the rational design of PROTACs. Furthermore, this review discusses the role of MS in the structural analysis of proteins and the formation of ternary complexes crucial for the activity of PROTACs. The synergy between MS and PROTAC technology holds the promise of groundbreaking advancements in drug discovery by deepening our understanding of the underlying mechanisms that govern PROTAC drug action, thereby promoting the development of innovative strategies for disease treatment.
靶向蛋白质降解技术的出现，尤其是蛋白酶靶向嵌合体（PROTAC），能够选择性地消除靶蛋白，并为各种疾病的治疗开辟了新途径。本综述深入探讨了质谱（MS）在PROTAC发展中的关键作用。基于质谱的方法是鉴定PROTAC靶点、验证其疗效、阐明泛素化位点和蛋白质降解动力学的宝贵工具。这些见解极大地丰富了我们对作用机制的理解，并有助于PROTAC的合理设计。此外，本综述还讨论了质谱在蛋白质结构分析以及对PROTAC活性至关重要的三元复合物形成中的作用。质谱与PROTAC技术之间的协同作用有望通过加深我们对PROTAC药物作用潜在机制的理解，在药物发现方面取得突破性进展，从而促进疾病治疗创新策略的发展。
