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Synthesis and Microarray-Assisted Binding Studies of Core Xylose and Fucose Containing N‑Glycans
journal contribution
posted on 2015-05-15, 00:00 authored by Katarzyna Brzezicka, Begoña Echeverria, Sonia Serna, Angela van Diepen, Cornelis
H. Hokke, Niels-Christian ReichardtThe synthesis of a collection of
33 xylosylated and core-fucosylated
N-glycans found only in nonmammalian organisms such as plants and
parasitic helminths has been achieved by employing a highly convergent
chemo-enzymatic approach. The influence of these core modifications
on the interaction with plant lectins, with the human lectin DC-SIGN
(Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing
Nonintegrin), and with serum antibodies from schistosome-infected
individuals was studied. Core xylosylation markedly reduced or completely
abolished binding to several mannose-binding plant lectins and to
DC-SIGN, a C-type lectin receptor present on antigen presenting cells.
Employing the synthetic collection of core-fucosylated and core-xylosylated
N-glycans in the context of a larger glycan array including structures
lacking these core modifications, we were able to dissect core xylose
and core fucose specific antiglycan antibody responses in S. mansoni infection sera, and we observed clear and immunologically
relevant differences between children and adult groups infected with
this parasite. The work presented here suggests that, quite similar
to bisecting N-acetylglucosamine, core xylose distorts the conformation
of the unsubstituted glycan, with important implications for the immunogenicity
and protein binding properties of complex N-glycans.