Aryl fucosides: synthesis and evaluation of their binding affinity towards the DC-SIGN receptor.

Abstract

DC-SIGN, a C-type lectin receptor expressed on antigen presenting cells, is crucial for pathogen recognition and immune modulation. While most glycomimetic DC-SIGN ligands are mannose-based, fucose-based ligands offer enhanced selectivity, potentially reducing off-target effects. This study reports the stereoselective synthesis of aryl α-L-fucosides and their binding affinity for DC-SIGN. Using ¹H-¹⁵N HSQC NMR and a competition assay, we identified 3-trifluoromethylphenyl α-L-fucoside as the best ligand, exhibiting both K_D and IC₅₀ values in a three-digit micromolar range and binding not only to the canonical site, but also to a secondary allosteric site.