SYNTHESIS OF FUCOSE-BASED LIGANDS FOR DC-SIGN.

DC-SIGN is a C-type lectin that is expressed in dendritic cells and that is involved in a number of infection processes such as HIV or Ebola. Within the scope of this work a library of monovalent, fucose-based ligands was synthesised to block DC-SIGN. The structures originate from three scaffolds containing 2-aminocyclohexane carboxylic acid in different configurations. The compounds were tested by means of SPR competition assays and were found to be similar to the natural ligand Lewis X in terms of affinity for DC-SIGN. On the one hand, the most potent ligand, and on the other hand, the most accessible ligand were selected for further functionalisation and polyvalent presentation by the attachment to dendrimers. The increased valency resulted in an improved affinity by up to one order of magnitude in comparison with the monomeric structure. Moreover, the functionalised monomers were used for the fabrication of glycan arrays and were screened with several commercially available lectins. Strongest binding could be detected with the lectin from the bacterial phytopathogen Ralstonia solanacearum.