Glycosylation is an important posttranslational modifier of proteins and lipid conjugates critical for the stability and function of these macromolecules. Particularly important are N-linked glycans attached to asparagine residues in proteins. N-glycans have well-defined roles in protein folding, cellular trafficking and signal transduction, and alterations to them are implicated in a variety of diseases. However, the non-template driven biosynthesis of these N-glycans leads to significant structural diversity, making it challenging to identify the most biologically and clinically relevant species using conventional analyses. Advances in mass spectrometry instrumentation and data acquisition, as well as in enzymatic and chemical sample preparation strategies, have positioned mass spectrometry approaches as powerful analytical tools for the characterization of glycosylation in health and disease. Imaging mass spectrometry expands upon these strategies by capturing the spatial component of a glycan's distribution in-situ, lending additional insight into the organization and function of these molecules. Herein we review the ongoing evolution of glycan imaging mass spectrometry beginning with widely adopted tissue imaging approaches and expanding to other matrices and sample types with potential research and clinical implications. Adaptations of these techniques, along with their applications to various states of disease, are discussed. Collectively, glycan imaging mass spectrometry analyses broaden our understanding of the biological and clinical relevance of N-glycosylation to human disease.

中文翻译：

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聚糖成像质谱的应用和持续发展

糖基化是蛋白质和脂质缀合物的重要翻译后修饰剂，对于这些大分子的稳定性和功能至关重要。特别重要的是连接到蛋白质中天冬酰胺残基上的 N 连接聚糖。N-聚糖在蛋白质折叠、细胞运输和信号转导中具有明确的作用，其改变与多种疾病有关。然而，这些 N-聚糖的非模板驱动生物合成导致了显着的结构多样性，使得使用传统分析来识别最具生物学和临床相关性的物种变得具有挑战性。质谱仪器和数据采集以及酶促和化学样品制备策略的进步，使质谱方法成为表征健康和疾病中糖基化的强大分析工具。成像质谱法通过原位捕获聚糖分布的空间成分来扩展这些策略，从而进一步了解这些分子的组织和功能。在此，我们回顾了聚糖成像质谱的持续发展，从广泛采用的组织成像方法开始，扩展到具有潜在研究和临床意义的其他基质和样品类型。讨论了这些技术的适应性及其在不同疾病状态下的应用。总的来说，聚糖成像质谱分析拓宽了我们对 N-糖基化与人类疾病的生物学和临床相关性的理解。