β-Mannosyl Triazoles as Mimics of Galactosyl Galectin-3 and Galectin-9 N-Terminal Domain Inhibitors

Mannosyl β-C-1 amidotriazoles have previously been reported to have higher selectivity for galectin-9N (N-terminal domain) than the corresponding galactoside C3 amidotriazoles have, which were more selective for galectin-3. This study further investigated this by synthesis of mono- and bis-aryltriazolyl mannoside analogues to known high-affinity galectin-3 galactosyl-derived inhibitors. Following synthesis, affinity measurements using competititve fluorescence polarization assays were performed which indicated low affinity of the bis-aryltriazolyl mannosyls, while the mono-aryltriazolyl mannosyls analogs possessed improved affinity, albeit with lower and selectivity. From conformational calculations it was implied that the weak-binding bis-aryltriazolyl mannosyl analogues do not find the same conformation and binding pose as the parent galactoside compounds.