光亲和探针在化学蛋白质组学中的靶标发现与应用突破

Photoaffinity Probes in Chemoproteomics: Breakthroughs in Target Discovery and Applications

关键词:  化学蛋白质组学  光亲和探针  靶标发现

Key words:  chemoproteomics  photoaffinity probes  target discovery

摘要:

药物靶标发现是创新药物研发的核心环节,然而传统靶标发现方法在捕获瞬时、低亲和力或低丰度蛋白的相互作用方面存在一定局限性,化学蛋白质组学技术的兴起为这一瓶颈提供了突破性解决方案。本篇综述介绍了近年来基于化学蛋白质组学的光交联技术在小分子化合物靶点发现领域上的重要进展,重点介绍了该技术通过整合光亲和探针、生物正交标记与高分辨质谱等技术实现对活细胞内小分子化合物-靶标互作网络的全景式解析。这些技术的突破为发现新型治疗靶标,揭示药物作用机制开辟了新途径,为新药研发提供更多精准有效的用药建议。

Abstract:

Drug target discovery represents a central step in innovative drug discovery. However, conventional approaches for target identification face limitations in capturing transient, low-affinity, or low-abundance protein interactions. The emergence of chemical proteomics has provided breakthrough solutions to this bottleneck. This review highlights recent advances in photo-crosslinking technologies based on chemical proteomics for identifying targets of small molecule compounds. We focus on how the integration of photoaffinity probes, bioorthogonal labeling, and high-resolution mass spectrometry enables global mapping of small molecule compound-target interaction networks within live cells. These technological breakthroughs pave new avenues for discovering novel therapeutic targets, elucidating drug mechanisms of action, and offering precise and effective therapeutic strategies for drug discovery.