Binding Evaluation of Pradimicins for Oligomannose Motifs from Fungal Mannans

Pradimicins (PRMs) are a unique family of natural products that exhibit antifungal activity via binding to cell wall mannans of fungi. Although their mannan-targeted antifungal action has attracted considerable interest, there is still only limited knowledge as to how PRMs bind to mannans. In this study, we evaluated the relative binding affinity of PRMs for synthetic oligomannoses, which reflect the structural motifs characteristic of cell wall mannans from Candida albicans. Two complementary binding assays revealed a strong preference of PRMs for branched oligomannose motifs with multiple mannose residues at the non-reducing ends. In addition, oligomannose mimics, in which two mannoses are bridged by polyethylene glycol spacers, were found to behave similarly to two-branched oligomannoses in both assays. These results indicate that PRMs preferentially bind to highly branched regions of fungal mannans via the simultaneous recognition of multiple terminal mannose residues.