Synthesis of branched-phosphodiester and mannose-centered fucosylated glycoclusters and their binding studies with Burkholderia ambifaria lectin (BambL)

Abstract

Five fucosylated glycoclusters exhibiting 4, 6 or 8 residues were synthesised with two different spatial environments based on mannose-centered and branched-phosphodiester scaffolds. Their synthesis was performed in solution using phosphoramidite chemistry to generate phosphodiester linkages, combined with Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). The multivalent ligands were evaluated for their ability to bind to Burkholderia ambifaria Lectin (BambL). Binding evaluation was performed through inhibition of hemagglutination (HIA), surface plasmon resonance (SPR) and isothermal titration microcalorimetry (ITC). All fucosylated glycoclusters exhibited a higher affinity to BambL than methyl α-L-fucoside. A dissociation constant of 43 nM was observed for the fucocluster exhibiting four residues with the branched-phosphodiester spatial environment corresponding to a 22-fold increase in comparison with methyl α-L-fucoside. These multivalent fucoclusters represent the first example of ligands of high affinity to BambL.