Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA.
AD Bio US, Takeda, Lexington, Massachusetts, 02421, USA.
Mass Spectrom Rev. 2024 Jan-Feb;43(1):166-192. doi: 10.1002/mas.21837. Epub 2023 Mar 16.
Chemical proteomics, which involves studying the covalent modifications of proteins by small molecules, has significantly contributed to our understanding of protein function and has become an essential tool in drug discovery. Mass spectrometry (MS) is the primary method for identifying and quantifying protein-small molecule adducts. In this review, we discuss various methods for measuring proteomic reactivity using MS and covalent proteomics probes that engage through reactivity-driven and proximity-driven mechanisms. We highlight the applications of these methods and probes in live-cell measurements, drug target identification and validation, and characterizing protein-small molecule interactions. We conclude the review with current developments and future opportunities in the field, providing our perspectives on analytical considerations for MS-based analysis of the proteomic reactivity landscape.
化学蛋白质组学涉及研究小分子对蛋白质的共价修饰，它极大地促进了我们对蛋白质功能的理解，并且已经成为药物发现的重要工具。质谱 (MS) 是鉴定和定量蛋白质-小分子加合物的主要方法。在这篇综述中，我们讨论了使用 MS 测量蛋白质组反应性的各种方法，以及通过反应性驱动和接近驱动机制结合的共价蛋白质组学探针。我们强调了这些方法和探针在活细胞测量、药物靶标鉴定和验证以及表征蛋白质-小分子相互作用方面的应用。我们以该领域当前的发展和未来的机遇为结尾，就基于 MS 的蛋白质组反应性图谱分析提供了我们对分析注意事项的看法。
