Synthesis of three trisaccharide congeners to investigate frame shifting of β1,2-mannan homo-oligomers in an antibody binding site Original Research Article

Homopolysaccharides such as the protective β1,2-mannan present in the cell wall of Candida albicans have the capability to bind to antibody in numerous frame shifted modes. A protective monoclonal antibody C3.1 binds this antigen and exhibits a unique binding profile where di and trisaccharides are the most potent inhibitors, while the intrinsic affinities of tetrasaccharide and larger oligomers dramatically decrease with increasing chain length. The design, synthesis and inhibitory activity of three β1,2-linked trisaccharide congeners is reported. Selective functional group modification was introduced at the terminal reducing or non-reducing mannose residues so that each trisaccharide would be capable of binding to antibody in only one of the possible frame shifted modes. Inhibition data show that C3.1 has the highest affinity for internally situated disaccharide epitopes but can bind the terminal non-reducing disaccharide of a trisaccharide epitope.