关键词: chemical biology chemical reporter chemoenzymatic labelling glycobiology glycosylation metabolic engineering

Mesh : Animals Glycomics / methods Glycoproteins / metabolism Glycosylation Glycosyltransferases / genetics metabolism Humans Mammals / metabolism Metabolic Engineering / methods Models, Chemical Molecular Probes / chemistry metabolism Molecular Structure Oligosaccharides / chemistry metabolism Polysaccharides / chemistry metabolism Proteomics / methods Staining and Labeling / methods

来  源:   DOI:10.1042/BST20200839   PDF(Pubmed)

Abstract:
Glycans play essential roles in a range of cellular processes and have been shown to contribute to various pathologies. The diversity and dynamic nature of glycan structures and the complexities of glycan biosynthetic pathways make it challenging to study the roles of specific glycans in normal cellular function and disease. Chemical reporters have emerged as powerful tools to characterise glycan structures and monitor dynamic changes in glycan levels in a native context. A variety of tags can be introduced onto specific monosaccharides via the chemical modification of endogenous glycan structures or by metabolic or enzymatic incorporation of unnatural monosaccharides into cellular glycans. These chemical reporter strategies offer unique opportunities to study and manipulate glycan functions in living cells or whole organisms. In this review, we discuss recent advances in metabolic oligosaccharide engineering and chemoenzymatic glycan labelling, focusing on their application to the study of mammalian O-linked glycans. We describe current barriers to achieving glycan labelling specificity and highlight innovations that have started to pave the way to overcome these challenges.
摘要:
聚糖在一系列细胞过程中发挥重要作用,并已被证明有助于各种病理。聚糖结构的多样性和动态性质以及聚糖生物合成途径的复杂性使得研究特定聚糖在正常细胞功能和疾病中的作用具有挑战性。化学报告分子已经成为表征聚糖结构和监测天然环境中聚糖水平动态变化的强大工具。通过内源性聚糖结构的化学修饰或通过将非天然单糖代谢或酶促掺入细胞聚糖,可以将多种标签引入到特定单糖上。这些化学报告策略提供了研究和操纵活细胞或整个生物体中的聚糖功能的独特机会。在这次审查中,我们讨论了代谢寡糖工程和化学酶聚糖标记的最新进展,重点是它们在哺乳动物O-连接聚糖研究中的应用。我们描述了目前实现聚糖标记特异性的障碍,并强调了已经开始为克服这些挑战铺平道路的创新。
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