Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200032, P. R. China.
Chem Commun (Camb). 2021 Jan 26;57(6):737-740. doi: 10.1039/d0cc06493a.
Mass spectrometry (MS) quantification has become an essential tool for both modern biology and translational medicine research. Data-independent acquisition (DIA) has emerged recently and combines the merits of data-dependent acquisition (DDA) methods and selected reaction monitoring (SRM) approaches. Unfortunately, making a quantitative comparison between samples in a single DIA injection is extremely restricted due to its poor compatibility with the traditional DDA labeling approach. As a consequence, a multiplex quantitative reagent suitable for the DIA strategy would be strongly desirable to improve these uninformative situations. As counterparts to traditional DDA quantitative reagents, such as tandem mass tags (TMT) and isobaric tags for relative and absolute quantification (iTRAQ), here, we have designed a novel mass-defect-based carbonyl activated tag (mdCAT) allowing the DIA method to quantify eight samples in parallel for the first time. The integration of the mdCATs with the DIA strategy can not only allow the popular and powerful merits of the DIA strategy, such as broad proteomic coverage, good reproducibility, and accuracy, but it can also eliminate spectral complexity due to their minuscule mass differences. In doing so, it offers new opportunities for the investigation of clinical samples, driving the field of DIA toward unprecedented multiplexing and improving its ability to search for diagnostic biomarkers.
质谱（MS）定量已成为现代生物学和转化医学研究的重要工具。数据非依赖性采集（DIA）最近出现，结合了数据依赖性采集（DDA）方法和选择反应监测（SRM）方法的优点。不幸的是，由于其与传统 DDA 标记方法的兼容性较差，因此在单个 DIA 注射中对样本进行定量比较受到极大限制。因此，需要一种适用于 DIA 策略的多路定量试剂，以改善这些无信息情况。作为传统 DDA 定量试剂的对应物，如串联质量标签（TMT）和相对和绝对定量的同重同位素标签（iTRAQ），在这里，我们设计了一种新型基于质量缺陷的羰基激活标签（mdCAT），首次允许 DIA 方法同时定量 8 个样本。将 mdCAT 与 DIA 策略相结合，不仅可以利用 DIA 策略的广泛的蛋白质组覆盖、良好的重现性和准确性等流行且强大的优点，还可以消除由于其微小的质量差异而导致的光谱复杂性。这样，它为临床样本的研究提供了新的机会，推动 DIA 领域实现前所未有的多路复用，并提高其寻找诊断生物标志物的能力。
