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.

TETRALEC, Artificial Tetrameric Lectins: A Tool to Screen Ligand and Pathogen Interactions

“…All constructs exhibited a similar trend in glycan recognition, high mannose and hybrid N-glycans being the preferential bound structures (Figure 6a). It is important to highlight that certain differences in binding were also observed, underlining the importance of geometrical presentation and distance between CRDs for the recognition of epitopes (Figure 6) [28]. Natural tetrameric DC-SIGNR ECD showed recognition towards mannose containing N-glycan structures presented on the microarray, in line with previous reported specificity.…”

Chemical Synthesis of Fucosylated Chondroitin Sulfate Tetrasaccharide with Fucosyl Branch at the 6-OH of GalNAc Residue

“…The compound 10 was obtained in a three-step reaction with aminogalactose hydrochloride as the starting material in 71% yield [23]. Subsequently, 10 was coupled with N-benzyl-benzylcarbamate protected aminopentyl linker L-1 [24] under N-iodosuccinimide (NIS) and TMSOTf conditions to give β-linked product 11 [25] in 91% yield. Then the acetyl groups were removed and a benzylidene group was formed between the C-4/C-6 hydroxyl groups to give the 3-OH unprotected aminogalactose acceptor 13 [25] (Scheme 3).…”

“…Subsequently, 10 was coupled with N-benzyl-benzylcarbamate protected aminopentyl linker L-1 [24] under N-iodosuccinimide (NIS) and TMSOTf conditions to give β-linked product 11 [25] in 91% yield. Then the acetyl groups were removed and a benzylidene group was formed between the C-4/C-6 hydroxyl groups to give the 3-OH unprotected aminogalactose acceptor 13 [25] (Scheme 3). In order to construct a 1,2-trans-β-glycosidic bond of 2-deoxy-β-D-galactopyranoside, phthaloyl (Phth) and trichloroethoxycarbonyl (Troc), through neighbouring group participation, are often used as amino-protecting groups [23].…”

Glycan microarrays from construction to applications

“…This lectin binds preferentially to high-mannose-type glycans and fucose-bearing sugars (e.g., Le a , Le b , Le x and Le y ). 45,[115][116][117][118] Thus, DC-SIGN has the ability to recognize pathogens that produce high-mannose or fucosylated glycans on their surfaces, such as the human immunodeficiency virus (HIV), hepatitis C virus (HCV), Ebola virus, Mycobacterium tuberculosis, Candida albicans, Helicobacter pylori and Leishmania parasites. DC-SIGNR, a DC-SIGN homologue expressed on the surface of endothelial cells, is the C-type lectin that interacts with pathogenic glycans without mediating endocytosis.…”