Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109, USA.
Curr Opin Chem Biol. 2013 Oct;17(5):809-17. doi: 10.1016/j.cbpa.2013.06.019. Epub 2013 Jul 12.
Mass spectrometry (MS) plays a number of key roles in the discovery and development phases for modern pharmaceutical compounds, ranging from the assessment of protein-ligand binding to biomarker discovery. Historically, however, MS has had a relatively limited role in the drug discovery process in comparison to high-throughput fluorescence and radiometric screens. This picture may be changing, however, as many presumptive protein targets are coupled to human disease pathways through specific protein-protein interactions and protein conformations, rather than enzyme activities. This fact will likely drive the development of high-throughput analytical tools that put a stronger emphasis on the structural information content produced in a screen. Here we summarize recent developments surrounding ion mobility-mass spectrometry (IM-MS), one such MS-based tool that is capable of rapidly measuring changes in protein structure, oligomeric state, and binding stoichiometry from complex mixtures at relatively low concentrations.
质谱（MS）在现代药物化合物的发现和开发阶段发挥了许多关键作用，从评估蛋白配体结合到生物标志物发现。然而，与高通量荧光和放射性筛选相比，MS 在药物发现过程中一直扮演着相对有限的角色。然而，这种情况可能正在发生变化，因为许多假定的蛋白质靶标通过特定的蛋白质-蛋白质相互作用和蛋白质构象与人类疾病途径相关，而不是酶活性。这一事实很可能推动高通量分析工具的发展，这些工具更加强调筛选中产生的结构信息含量。在这里，我们总结了围绕离子淌度-质谱（IM-MS）的最新进展，这是一种基于 MS 的工具，能够快速测量复杂混合物中相对低浓度下蛋白质结构、寡聚状态和结合化学计量的变化。
