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Chemo‐Enzymatic Synthesis of S. mansoni O‐Glycans and Their Evaluation as Ligands for C‐Type Lectin Receptors MGL, DC‐SIGN, and DC‐SIGNR
Author(s) -
Pham Julie,
Hernandez Alvaro,
Cioce Anna,
Achilli Silvia,
Goti Giulio,
Vivès Corinne,
Thepaut Michel,
Bernardi Anna,
Fieschi Franck,
Reichardt NielsChristian
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202000291
Subject(s) - dc sign , glycan , schistosoma mansoni , fucosylation , lectin , fucose , mucin , chemistry , biochemistry , receptor , recombinant dna , biology , microbiology and biotechnology , glycoprotein , antigen , dendritic cell , immunology , schistosomiasis , gene , helminths
Due to their interactions with C‐type lectin receptors (CLRs), glycans from the helminth Schistosoma mansoni represent promising leads for treatment of autoimmune diseases, allergies or cancer. We chemo‐enzymatically synthesized nine O‐glycans based on the two predominant O‐glycan cores observed in the infectious stages of schistosomiasis, the mucin core 2 and the S. mansoni core. The O‐glycans were fucosylated next to a selection of N ‐glycans directly on a microarray slide using a recombinant fucosyltransferase and GDP‐fucose or GDP‐6‐azidofucose as donor. Binding assays with fluorescently labelled human CLRs DC‐SIGN, DC‐SIGNR and MGL revealed the novel O‐glycan O8 as the best ligand for MGL from our panel. Significant binding to DC‐SIGN was also found for azido‐fucosylated glycans. Contrasting binding specificities were observed between the monovalent carbohydrate recognition domain (CRD) and the tetravalent extracellular domain (ECD) of DC‐SIGNR.