Aryl fucosides: synthesis and evaluation of their binding affinity towards the DC-SIGN receptor
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 <sup>1</sup>H-<sup>15</sup>N HSQC NMR and a competition assay, we identified 3-trifluoromethylphenyl α-L-fucoside as the best ligand, exhibiting both <i>K</i><sub>D</sub> and IC<sub>50</sub> values in a three-digit micromolar range and binding not only to the canonical site, but also to a secondary allosteric site.
Authors
- Petra Ménová (ORCID: https://orcid.org/0000-0002-8450-194X)
- RP Chavan
- Jonathan Lefèbre (ORCID: https://orcid.org/0000-0001-8505-2181)
- Christoph Rademacher
- Maurice Besch (ORCID: https://orcid.org/0000-0001-9242-0261)
Institutions
- University of Vienna (AT)
- Max Perutz Labs (AT)
- Vienna Biocenter (AT)
- University of Chemistry and Technology, Prague (CZ)
Publication Details
- Journal
- Organic & Biomolecular Chemistry
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d5ob00472a
- Primary Topic
- Carbohydrate Chemistry and Synthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Fonds National de la Recherche Luxembourg
- Max-Planck-Gesellschaft
- Horizon 2020 Framework Programme