Chemoproteomics is an invaluable tool to discover protein targets from phenotypic assays and to understand on- and off-target engagement of potential therapeutic compounds. Highlighted in this technology perspective is our view on how improvements in mass spectrometry (MS)-based proteomics technology have dramatically impacted chemoproteomics. Improvements in sample preparation, MS instrumentation, data acquisition, and quantification strategies have enabled medicinal chemists, chemical biologists, and mass spectrometrists to develop new chemoproteomic experiments and improve existing methods. As a result of improvements in MS, we will detail how bead-based affinity capture and activity-based proteome profiling methods have been reduced from multiple LC–MS runs for samples and controls down to a single LC–MS run each for sample and control. With improvements in scan duty cycle and sensitivity, sufficient depth of proteome coverage can be obtained for capture-free methods, which do not utilize an enrichment step.

中文翻译：

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基于质谱的技术和策略对化学蛋白质组学作为药物发现工具的影响

化学蛋白质组学是一种非常有价值的工具，可以从表型分析中发现蛋白质靶标，并了解潜在治疗化合物的靶标和靶标脱离。在此技术观点中突出显示的是我们对基于质谱（MS）的蛋白质组学技术的改进如何对化学蛋白质组学产生巨大影响的观点。样品制备，MS仪器，数据采集和定量策略的改进使药物化学家，化学生物学家和质谱师能够开发新的化学旋转实验并改进现有方法。由于MS的改进，我们将详细介绍如何将基于珠子的亲和捕获和基于活性的蛋白质组谱分析方法从针对样品和对照的多个LC-MS运行降低为针对样品和对照的单个LC-MS运行。