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当前用于复杂糖蛋白质组学的技术及其在生物学/疾病驱动的糖蛋白质组学中的应用。

Current Technologies for Complex Glycoproteomics and Their Applications to Biology/Disease-Driven Glycoproteomics.

机构信息

Biotechnology Research Institute for Drug Discovery , National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono , Tsukuba , Ibaraki 305-8568 , Japan.

Copenhagen Center for Glycomics , University of Copenhagen , Blegdamsvej 3 , Copenhagen 2200 , Denmark.

出版信息

J Proteome Res. 2018 Dec 7;17(12):4097-4112. doi: 10.1021/acs.jproteome.8b00515. Epub 2018 Oct 25.

DOI:10.1021/acs.jproteome.8b00515
PMID:30359034
Abstract

Glycoproteomics is an important recent advance in the field of glycoscience. In glycomics, glycan structures are comprehensively analyzed after glycans are released from glycoproteins. However, a major limitation of glycomics is the lack of insight into glycoprotein functions. The Biology/Disease-driven Human Proteome Project has a particular focus on biological and medical applications. Glycoproteomics technologies aimed at obtaining a comprehensive understanding of intact glycoproteins, i.e., the kind of glycan structures that are attached to particular amino acids and proteins, have been developed. This Review focuses on the recent progress of the technologies and their applications. First, the methods for large-scale identification of both N- and O-glycosylated proteins are summarized. Next, the progress of analytical methods for intact glycopeptides is outlined. MS/MS-based methods were developed for improving the sensitivity and speed of the mass spectrometer, in parallel with the software for complex spectrum assignment. In addition, a unique approach to identify intact glycopeptides using MS1-based accurate masses is introduced. Finally, as an advance of glycomics, two approaches to provide the spatial distribution of glycans in cells are described, i.e., MS imaging and lectin microarray. These methods allow rapid glycomic profiling of different types of biological samples and thus facilitate glycoproteomics.

摘要

糖组学是糖科学领域的一项重要进展。在糖组学中,糖链结构在糖蛋白中的糖链被释放后被全面分析。然而,糖组学的一个主要局限性是缺乏对糖蛋白功能的深入了解。生物学/疾病驱动的人类蛋白质组计划特别关注生物和医学应用。糖蛋白质组学技术旨在全面了解完整的糖蛋白,即与特定氨基酸和蛋白质相连的糖链结构,已经开发出来。这篇综述重点介绍了这些技术的最新进展及其应用。首先,总结了大规模鉴定 N-和 O-糖基化蛋白的方法。接下来,概述了完整糖肽的分析方法的进展。基于 MS/MS 的方法被开发出来,以提高质谱仪的灵敏度和速度,同时也开发了用于复杂谱分配的软件。此外,还介绍了一种使用基于 MS1 的精确质量来鉴定完整糖肽的独特方法。最后,作为糖组学的一项进展,描述了两种在细胞中提供聚糖空间分布的方法,即 MS 成像和凝集素微阵列。这些方法允许对不同类型的生物样品进行快速糖组学分析,从而促进了糖蛋白质组学的发展。

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