Department of Biochemistry and Molecular Biology, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou 215123, China.
Bioanalytical Mass Spectrometry Group, Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.
Int J Mol Sci. 2022 Jan 30;23(3):1609. doi: 10.3390/ijms23031609.
Protein glycosylation governs key physiological and pathological processes in human cells. Aberrant glycosylation is thus closely associated with disease progression. Mass spectrometry (MS)-based glycoproteomics has emerged as an indispensable tool for investigating glycosylation changes in biological samples with high sensitivity. Following rapid improvements in methodologies for reliable intact glycopeptide identification, site-specific quantification of glycopeptide macro- and micro-heterogeneity at the proteome scale has become an urgent need for exploring glycosylation regulations. Here, we summarize recent advances in N- and O-linked glycoproteomic quantification strategies and discuss their limitations. We further describe a strategy to propagate MS data for multilayered glycopeptide quantification, enabling a more comprehensive examination of global and site-specific glycosylation changes. Altogether, we show how quantitative glycoproteomics methods explore glycosylation regulation in human diseases and promote the discovery of biomarkers and therapeutic targets.
蛋白质糖基化调控着人类细胞中的关键生理和病理过程。因此，异常的糖基化与疾病的进展密切相关。基于质谱（MS）的糖蛋白质组学已经成为一种不可或缺的工具，可用于高灵敏度地研究生物样本中的糖基化变化。在可靠的完整糖肽鉴定方法快速改进之后，在蛋白质组范围内对糖肽宏观和微观异质性的特异性定量成为探索糖基化调控的迫切需求。在这里，我们总结了 N-和 O-连接糖蛋白质组定量策略的最新进展，并讨论了它们的局限性。我们进一步描述了一种用于多层糖肽定量的 MS 数据扩展策略，能够更全面地研究全局和特异性糖基化变化。总之，我们展示了定量糖蛋白质组学方法如何在人类疾病中探索糖基化调控，并促进生物标志物和治疗靶点的发现。
