基于质谱的N-糖蛋白分析进展  

Progresses of mass spectrometry-based analysis of N-glycoproteins

作　　者：田志新[1] TIAN Zhixin(School of Chemical Science and Engineering,TongJi University,Shanghai 200092,China)

机构地区：[1]同济大学化学科学与工程学院,上海200092

出　　处：《中国药科大学学报》2023年第6期662-673,共12页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.22074105,No.21775110,No.21575104)。

摘　　要：N-连接糖基化是蛋白质上常见的翻译后修饰,在修饰位点上具有跟其他小分子修饰(如甲基化、乙酰化、磷酸化)同样的宏观不均一性,也就是蛋白质氨基酸序列上具有多个潜在的修饰位点。但相对于小分子修饰单一的结构,N-糖基化修饰具有来自不同单糖组成,序列结构、链接结构、异头异构,立体构象等多个结构维度的数以万计的结构。这使得N-糖基化在修饰位点上具有额外的微观不均一性,也就是说同一个N-糖基化位点可以以一定的化学计量比修饰不同的糖链。N-糖基化修饰以位点和结构特异的方式调控N-糖蛋白的结构和功能,疾病条件下差异表达的N-糖基化需通过位点和结构特异的定量分析来表征。本文主要介绍最新发展水平的基于质谱的位点和结构特异定量N-糖蛋白质组学及在生物医学中的应用。N-linked glycosylation is a common post-translational modification on proteins,which exhibits the same macro-heterogeneity of modification site as other small molecule modifications(such as methylation,acetylation,phosphorylation),i.e.,the amino acid sequence of a protein has multiple putative modification sites.However,compared to small molecule modifications with single structures,N-glycosylation modification have tens of thousands of structures from multiple structural dimensions such as different monosaccharide compositions,sequence structures,linking structures,isomerism,and three-dimensional conformation.This results in additional micro-heterogeneity of modification site of N-glycosylation,i.e.,the same N-glycosylation site can be modified with different glycans with a certain stoichiometric ratio.N-glycosylation modification regulates the structure and function of N-glycoproteins in a site-and structure-specific manner,and differential expression of N-glycosylation under disease conditions needs to be characterized through site-and structure-specific quantitative analysis.This article mainly introduces the latest development of mass spectrometry-based site-and structure-specific quantitative N-glycoproteomics and its applications in biomedical fields.

关 键 词：N-糖蛋白 糖基化位点 糖链结构 定性 定量 

分 类 号：R593[医药卫生—内科学]