Jump to main content
Jump to site search


Polyvalent C-glycomimetics based on L-fucose or D-mannose as potent DC-SIGN antagonists

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, IC50 17 µM; D-manno, IC50 12 µM). For the rest of glycodendrimers with L-fucose or D-mannose attached by 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.

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 10 Feb 2017, accepted on 10 Apr 2017 and first published on 12 Apr 2017


Article type: Paper
DOI: 10.1039/C7OB00322F
Citation: Org. Biomol. Chem., 2017, Accepted Manuscript
  •   Request permissions

    Polyvalent C-glycomimetics based on L-fucose or D-mannose as potent DC-SIGN antagonists

    B. Bertolotti, I. Sutkeviciute, M. Ambrosini, R. Ribeiro-Viana, J. Rojo, F. Fieschi, H. Dvorakova, M. Kašáková, K. Parkan, M. Hlaváčková, K. Novakova and J. Moravcova, Org. Biomol. Chem., 2017, Accepted Manuscript , DOI: 10.1039/C7OB00322F

Search articles by author