1. Polyvalent C-glycomimetics based on l-fucose or d-mannose as potent DC-SIGN antagonists.
- Author
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Bertolotti B, Sutkeviciute I, Ambrosini M, Ribeiro-Viana R, Rojo J, Fieschi F, Dvořáková H, Kašáková M, Parkan K, Hlaváčková M, Nováková K, and Moravcová J
- Subjects
- Inhibitory Concentration 50, Biomimetic Materials chemistry, Biomimetic Materials pharmacology, Cell Adhesion Molecules antagonists & inhibitors, Fucose chemistry, Lectins, C-Type antagonists & inhibitors, Mannose chemistry, Receptors, Cell Surface antagonists & inhibitors
- Abstract
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, IC
50 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.- Published
- 2017
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