Selective bioorthogonal probe for N-glycan hybrid structures.

Autor: Mukherjee MM; Laboratory of Cell and Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA., Biesbrock D; Laboratory of Cell and Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA., Abramowitz LK; Laboratory of Cell and Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA., Pavan M; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD, USA., Kumar B; Complex Carbohydrate Research Center, The University of Georgia, Athens, GA, USA., Walter PJ; Clinical Mass Spectrometry Core, NIDDK, National Institutes of Health, Bethesda, MD, USA., Azadi P; Complex Carbohydrate Research Center, The University of Georgia, Athens, GA, USA., Jacobson KA; Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD, USA., Hanover JA; Laboratory of Cell and Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA. johnh@bdg8.niddk.nih.gov.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2024 Oct 28. Date of Electronic Publication: 2024 Oct 28.
DOI: 10.1038/s41589-024-01756-5
Abstrakt: 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.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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