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Issue 18, 2017
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Polyvalent C-glycomimetics based on l-fucose or d-mannose as potent DC-SIGN antagonists

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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 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.

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

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Supplementary files

Article information


Submitted
10 Feb 2017
Accepted
10 Apr 2017
First published
12 Apr 2017

Org. Biomol. Chem., 2017,15, 3995-4004
Article type
Paper

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. Dvořáková, M. Kašáková, K. Parkan, M. Hlaváčková, K. Nováková and J. Moravcová, Org. Biomol. Chem., 2017, 15, 3995
DOI: 10.1039/C7OB00322F

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