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Custom Glycosylation of Cells and Proteins Using Cyclic Carbamate-Derivatized Oligosaccharides


Whitehead, Marek W J; Khanzhin, Nikolay; Borsig, Lubor; Hennet, Thierry (2017). Custom Glycosylation of Cells and Proteins Using Cyclic Carbamate-Derivatized Oligosaccharides. Cell Chemical Biology, 24(11):1336-1346.e3.

Abstract

The structural complexity of glycosylation restrains the functional characterization of glycans. We present a versatile carbohydrate ligation technique based on the reaction of cyclic carbamates with primary amines. Cyclic-carbamate-derivatized carbohydrates can be added to primary amine-containing molecules in aqueous solution to yield glycoconjugates. This method enabled the presentation of carbohydrate epitopes on live animal cells, as shown by the acquisition of E-selectin binding sites on mouse MC-38 cells decorated with 3-fucosyllactose or 3-fucosyl-3-sialyllactose. Ligation of 3- and 6-sialyllactose to Escherichia coli demonstrated the importance of sialic acid linkages in regulating complement factor H binding. Proteins were modified with oligosaccharides to study their role in stimulating cytokine secretion by dendritic cells, thus pointing to interactions between glycoproteins and phosphoinositide 3-kinase signaling in controlling interleukin-12, tumor necrosis factor alpha and interleukin-1β release. Overall, cyclic-carbamate-mediated ligation is useful to study the biology of carbohydrate epitopes on proteins and on cell membranes.

Abstract

The structural complexity of glycosylation restrains the functional characterization of glycans. We present a versatile carbohydrate ligation technique based on the reaction of cyclic carbamates with primary amines. Cyclic-carbamate-derivatized carbohydrates can be added to primary amine-containing molecules in aqueous solution to yield glycoconjugates. This method enabled the presentation of carbohydrate epitopes on live animal cells, as shown by the acquisition of E-selectin binding sites on mouse MC-38 cells decorated with 3-fucosyllactose or 3-fucosyl-3-sialyllactose. Ligation of 3- and 6-sialyllactose to Escherichia coli demonstrated the importance of sialic acid linkages in regulating complement factor H binding. Proteins were modified with oligosaccharides to study their role in stimulating cytokine secretion by dendritic cells, thus pointing to interactions between glycoproteins and phosphoinositide 3-kinase signaling in controlling interleukin-12, tumor necrosis factor alpha and interleukin-1β release. Overall, cyclic-carbamate-mediated ligation is useful to study the biology of carbohydrate epitopes on proteins and on cell membranes.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Clinical Biochemistry, Molecular Medicine, Biochemistry, Molecular Biology, Pharmacology, Drug Discovery
Language:English
Date:16 November 2017
Deposited On:09 Jan 2018 15:44
Last Modified:19 Aug 2018 12:29
Publisher:Cell Press (Elsevier)
ISSN:2451-9456
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.chembiol.2017.08.012
PubMed ID:28943358
Project Information:
  • : FunderSNSF
  • : Grant ID314730_172880
  • : Project TitleRegulatory functions of milk oligosaccharides

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