Zou Mingjie, Zhou Haiyuan, Gu Letian, Zhang Jingzi, Fang Lei
State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing 210093, China.
Biology (Basel). 2024 Jul 23;13(8):555. doi: 10.3390/biology13080555.
Throughout the human lifespan, from conception to the end of life, small molecules have an intrinsic relationship with numerous physiological processes. The investigation into small-molecule targets holds significant implications for pharmacological discovery. The determination of the action sites of small molecules provide clarity into the pharmacodynamics and toxicological mechanisms of small-molecule drugs, assisting in the elucidation of drug off-target effects and resistance mechanisms. Consequently, innovative methods to study small-molecule targets have proliferated in recent years, with chemical proteomics standing out as a vanguard development in chemical biology in the post-genomic age. Chemical proteomics can non-selectively identify unknown targets of compounds within complex biological matrices, with both probe and non-probe modalities enabling effective target identification. This review attempts to summarize methods and illustrative examples of small-molecule target identification via chemical proteomics. It delves deeply into the interactions between small molecules and human biology to provide pivotal directions and strategies for the discovery and comprehension of novel pharmaceuticals, as well as to improve the evaluation of drug safety.
在人类的整个生命周期中，从受孕到生命结束，小分子与众多生理过程有着内在联系。对小分子靶点的研究对药物发现具有重要意义。确定小分子的作用位点有助于阐明小分子药物的药效学和毒理学机制，辅助阐释药物的脱靶效应和耐药机制。因此，近年来研究小分子靶点的创新方法不断涌现，化学蛋白质组学作为后基因组时代化学生物学的前沿发展脱颖而出。化学蛋白质组学能够非选择性地识别复杂生物基质中化合物的未知靶点，探针法和非探针法都能有效识别靶点。本综述试图总结通过化学蛋白质组学鉴定小分子靶点的方法及实例。它深入探究小分子与人类生物学之间的相互作用，为新型药物的发现和理解提供关键方向和策略，同时改善药物安全性评估。
