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-Pr(2)-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.
Selective bioorthogonal probe for N-glycan hybrid structures.
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作者:Mukherjee Mana Mohan, Biesbrock Devin, Abramowitz Lara K, Pavan Matteo, Kumar Bhoj, Walter Peter J, Azadi Parastoo, Jacobson Kenneth A, Hanover John A
| 期刊: | Nature Chemical Biology | 影响因子: | 13.700 |
| 时间: | 2025 | 起止号: | 2025 May;21(5):681-692 |
| doi: | 10.1038/s41589-024-01756-5 | ||
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