Chemoenzymatic Synthesis of Complex N-Glycans of the Parasite S. mansoni to Examine the Importance of Epitope Presentation on DC-SIGN recognition.

Autor: Srivastava AD; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Bijvoet Center for Biomolecular Research, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands., Unione L; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Bijvoet Center for Biomolecular Research, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands., Bunyatov M; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Bijvoet Center for Biomolecular Research, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands., Gagarinov IA; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Bijvoet Center for Biomolecular Research, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands., Delgado S; Molecular Recognition and Host-Pathogen Interactions, CIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, Building 800, 48162, Derio, Bizkaia, Spain., Abrescia NGA; Molecular Recognition and Host-Pathogen Interactions, CIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, Building 800, 48162, Derio, Bizkaia, Spain.; Ikerbasque, Basque Foundation for Science, 48013, Bilbao, Bizkaia, Spain., Ardá A; Molecular Recognition and Host-Pathogen Interactions, CIC bioGUNE, Basque Research and Technology Alliance, BRTA, Bizkaia Technology Park, Building 800, 48162, Derio, Bizkaia, Spain.; Ikerbasque, Basque Foundation for Science, 48013, Bilbao, Bizkaia, Spain., Boons GJ; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Bijvoet Center for Biomolecular Research, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.; Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens, GA, 30602, USA.; Department of Chemistry, University of Georgia, Athens, GA, 30602, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Aug 23; Vol. 60 (35), pp. 19287-19296. Date of Electronic Publication: 2021 Jul 16.
DOI: 10.1002/anie.202105647
Abstrakt: The importance of multivalency for N-glycan-protein interactions has primarily been studied by attachment of minimal epitopes to artificial multivalent scaffold and not in the context of multi-antennary glycans. N-glycans can be modified by bisecting GlcNAc, core xylosides and fucosides, and extended N-acetyl lactosamine moieties. The impact of such modifications on glycan recognition are also not well understood. We describe here a chemoenzymatic methodology that can provide N-glycans expressed by the parasitic worm S. mansoni having unique epitopes at each antenna and containing core xyloside. NMR, computational and electron microscopy were employed to investigate recognition of the glycans by the human lectin DC-SIGN. It revealed that core xyloside does not influence terminal epitope recognition. The multi-antennary glycans bound with higher affinity to DC-SIGN compared to mono-valent counterparts, which was attributed to proximity-induced effective concentration. The multi-antennary glycans cross-linked DC-SIGN into a dense network, which likely is relevant for antigen uptake and intracellular routing.
(© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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