title: Synthesis and microarray-assisted binding studies of core xylose and fucose containing N-glycans.
abstract: The 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.
authors: †Glycotechnology Laboratory, CIC biomaGUNE, Paseo Miramón 182, 20009 San Sebastian, Spain.
authors: Katarzyna
authors: K
authors: Brzezicka
authors: †Glycotechnology Laboratory, CIC biomaGUNE, Paseo Miramón 182, 20009 San Sebastian, Spain.
authors: Begoña
authors: B
authors: Echeverria
authors: †Glycotechnology Laboratory, CIC biomaGUNE, Paseo Miramón 182, 20009 San Sebastian, Spain.
authors: Sonia
authors: S
authors: Serna
authors: ‡Parasite Glycobiology Group, Department of Parasitology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors: Angela
authors: A
authors: van Diepen
authors: ‡Parasite Glycobiology Group, Department of Parasitology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors: Cornelis H
authors: CH
authors: Hokke
authors: †Glycotechnology Laboratory, CIC biomaGUNE, Paseo Miramón 182, 20009 San Sebastian, Spain.|§CIBER BBN, Paseo Miramón 182, 20009 San Sebastian, Spain.
authors: Niels-Christian
authors: NC
authors: Reichardt
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood; D002240:Carbohydrate Sequence; D005643:Fucose / Q000737:chemistry*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008969:Molecular Sequence Data; D010944:Plants / Q000737:chemistry; D011134:Polysaccharides / Q000138:chemical synthesis / Q000737:chemistry*; D012552:Schistosomiasis / Q000276:immunology; D014994:Xylose / Q000737:chemistry*
chemical_list: D000913:Antibodies, Protozoan; D011134:Polysaccharides; D005643:Fucose; D014994:Xylose