Polyvalent C-glycomimetics based on l-fucose or d-mannose as potent DC-SIGN antagonists

Org Biomol Chem. 2017 May 10;15(18):3995-4004. doi: 10.1039/c7ob00322f.


The C-type lectin DC-SIGN expressed on immature dendritic cells is a promising target for antiviral drug development. Previously, we have demonstrated that mono- and divalent C-glycosides based on d-manno and l-fuco configurations are promising DC-SIGN ligands. Here, we described the convergent synthesis of C-glycoside dendrimers decorated with 4, 6, 9, and 12 α-l-fucopyranosyl units and with 9 and 12 α-d-mannopyranosyl units. Their affinity against DC-SIGN was assessed by surface plasmon resonance (SPR) assays. For comparison, parent O-glycosidic dendrimers were synthesized and tested, as well. A clear increase of both affinity and multivalency effect was observed for C-glycomimetics of both types (mannose and fucose). However, when dodecavalent C-glycosidic dendrimers were compared, there was no difference in affinity regarding the sugar unit (l-fuco, IC50 17 μM; d-manno, IC50 12 μM). For the rest of glycodendrimers with l-fucose or d-mannose attached by the O- or C-glycosidic linkage, C-glycosidic dendrimers were significantly more active. These results show that in addition to the expected physiological stability, the biological activity of C-glycoside mimetics is higher in comparison to the corresponding O-glycosides and therefore these glycomimetic multivalent systems represent potentially promising candidates for targeting DC-SIGN.

MeSH terms

  • Biomimetic Materials / chemistry*
  • Biomimetic Materials / pharmacology*
  • Cell Adhesion Molecules / antagonists & inhibitors*
  • Fucose / chemistry*
  • Inhibitory Concentration 50
  • Lectins, C-Type / antagonists & inhibitors*
  • Mannose / chemistry*
  • Receptors, Cell Surface / antagonists & inhibitors*


  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Fucose
  • Mannose