Mass Spectrometry-Based Chemical and Enzymatic Methods for Global Analysis of Protein Glycosylation

作者：Haopeng Xiao, Suttipong Suttapitugsakul, Fangxu Sun, Ronghu Wu · 发表于：Accounts of Chemical Research · 年份：2018 · DOI：10.1021/acs.accounts.8b00200 · 被引用次数：96 · 研究领域：Glycosylation and Glycoproteins Research、Carbohydrate Chemistry and Synthesis、Advanced Proteomics Techniques and Applications

Glycosylation is one of the most common protein modifications, and it is essential for mammalian cell survival. It often determines protein folding and trafficking, and regulates nearly every extracellular activity, including cell-cell communication and cell-matrix interactions. Aberrant protein glycosylation events are hallmarks of human diseases such as cancer and infectious diseases. Therefore, glycoproteins can serve as effective biomarkers for disease detection and targets for drug and vaccine development. Despite the importance of glycoproteins, global analysis of protein glycosylation (either glycoproteins or glycans) in complex biological samples has been a daunting task, and here we mainly focus on glycoprotein analysis using mass spectrometry (MS)-based bottom-up proteomics. Although the emergence of MS-based proteomics has provided a great opportunity to analyze glycoproteins globally, the low abundance of many glycoproteins and the heterogeneity of glycans dramatically increase the technical difficulties. In order to overcome these obstacles, considerable progress has been made in recent years, which has contributed to comprehensive analysis of glycoproteins. In our lab, we developed effective MS-based chemical and enzymatic methods to (1) globally analyze glycoproteins in complex biological samples, (2) target glycoproteins specifically on the surface of human cells, (3) systematically quantify glycoprotein and surface glycoprotein dynamics (the abundance changes...