Investigation of the Binding Affinity of a Broad Array of <span style="font-variant: small-caps">l</span>-Fucosides with Six Fucose-Specific Lectins of Bacterial and Fungal Origin

• Main Authors: Son Thai Le, Lenka Malinovska, Michaela Vašková, Erika Mező, Viktor Kelemen, Anikó Borbás, Petr Hodek, Michaela Wimmerová, Magdolna Csávás
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: Molecules
• Subjects: <span style="font-variant: small-caps">l</span>-fucosides; multivalency; lectins; glycoclusters; hemagglutination; cystic fibrosis
• Online Access: https://www.mdpi.com/1420-3049/24/12/2262

Series of multivalent &#945;-<span style="font-variant: small-caps;">l</span>-fucoside containing glycoclusters and variously decorated <span style="font-variant: small-caps;">l</span>-fucosides were synthesized to find potential inhibitors of fucose-specific lectins and study the structure-binding affinity relationships. Tri- and tetravalent fucoclusters were built using copper-mediated azide-alkyne click chemistry. Series of fucoside monomers and dimers were synthesized using various methods, namely glycosylation, an azide-alkyne click reaction, photoinduced thiol-en addition, and sulfation. The interactions between compounds with six fucolectins of bacterial or fungal origin were tested using a hemagglutination inhibition assay. As a result, a tetravalent, &#945;-<span style="font-variant: small-caps;">l</span>-fucose presenting glycocluster showed to be a ligand that was orders of magnitude better than a simple monosaccharide for tested lectins in most cases, which can nominate it as a universal ligand for studied lectins. This compound was also able to inhibit the adhesion of <i>Pseudomonas aeruginosa</i> cells to human epithelial bronchial cells. A trivalent fucocluster with a protected amine functional group also seems to be a promising candidate for designing glycoconjugates and chimeras.