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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

Abstract : 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.
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https://hal.archives-ouvertes.fr/hal-02974726
Contributor : Frank Thomas <>
Submitted on : Wednesday, November 25, 2020 - 11:17:09 AM
Last modification on : Wednesday, November 25, 2020 - 3:59:04 PM
Long-term archiving on: : Friday, February 26, 2021 - 6:48:36 PM

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Julie Pham, Alvaro Hernandez, Anna Cioce, Silvia Achilli, Giulio Goti, et al.. Chemo‐Enzymatic Synthesis of S. mansoni O‐Glycans and Their Evaluation as Ligands for C‐Type Lectin Receptors MGL, DC‐SIGN, and DC‐SIGNR. Chemistry - A European Journal, Wiley-VCH Verlag, 2020, 26 (56), pp.12818-12830. ⟨10.1002/chem.202000291⟩. ⟨hal-02974726⟩

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