Chemical biology research on targeting protein post-translational modifications

<p indent="0mm">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 cutting-edge 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.