Selective bioorthogonal probe for N-glycan hybrid structures

IF 12.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mana Mohan Mukherjee, Devin Biesbrock, Lara K. Abramowitz, Matteo Pavan, Bhoj Kumar, Peter J. Walter, Parastoo Azadi, Kenneth A. Jacobson, John A. Hanover
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引用次数: 0

Abstract

Metabolic incorporation of chemically tagged monosaccharides is a facile means of tagging cellular glycoproteins and glycolipids. However, since the monosaccharide precursors are often shared by several pathways, selectivity has been difficult to attain. For example, N-linked glycosylation is a chemically complex and ubiquitous posttranslational modification, with three distinct classes of GlcNAc-containing N-glycan structures: oligomannose, hybrid and complex. Here we describe the synthesis of 1,3-Pr2-6-OTs GlcNAlk (MM-JH-1) as a next-generation metabolic chemical reporter for the selective labeling of hybrid N-glycan structures. We first developed a general strategy for defining the selectivity of labeling with chemically tagged monosaccharides. We then applied this approach to establish that MM-JH-1 is selectively incorporated into hybrid N-glycans. Using this metabolic chemical reporter as a detection tool, we performed imaging and fractionation to define features of the intracellular localization and trafficking of target proteins bearing hybrid N-glycan structures.

Abstract Image

针对 N-聚糖杂交结构的选择性生物正交探针
化学标记单糖的代谢结合是标记细胞糖蛋白和糖脂的一种简便方法。然而,由于单糖前体通常由几种途径共享,因此很难实现选择性。例如,N-连接糖基化是一种化学上复杂且无处不在的翻译后修饰,有三类不同的含 GlcNAc 的 N-聚糖结构:低聚甘露糖、混合糖和复合糖。在这里,我们描述了 1,3-Pr2-6-OTs GlcNAlk(MM-JH-1)的合成过程,它是一种用于选择性标记混合 N-聚糖结构的下一代代谢化学报告物。我们首先开发了一种定义化学标记单糖标记选择性的一般策略。然后,我们应用这种方法确定 MM-JH-1 可选择性地结合到混合 N-聚糖中。利用这种新陈代谢化学报告物作为检测工具,我们进行了成像和分馏,以确定带有混合 N-聚糖结构的目标蛋白质在细胞内定位和运输的特征。
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来源期刊
Nature chemical biology
Nature chemical biology 生物-生化与分子生物学
CiteScore
23.90
自引率
1.40%
发文量
238
审稿时长
12 months
期刊介绍: Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision. The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms. Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.
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