Synthesis, modeling and binding affinity of an ester analogue of the terminal trisaccharide of the tumor-associated antigen globo H¹

The synthesis of the trisaccharide α-L-Fucp-(1→2)-β-D-Galp-(1→3)- β-D-Galp2AcOPr (3), mimicking the globo-H terminal trisaccharide unit (2), is described. The conformational properties of 3 were investigated with the aid of molecular mechanics energy minimizations, molecular dynamics simulations, and ¹H-NMR spectroscopic analysis and resulted in strict analogy with those of 2. Nevertheless, analysis of MBr1 binding to these compounds indicate that substitution of the acetamido group at C-2 with the ester group lowers the affinity, thus suggesting that the amide hydrogen atom of 2 is involved in intermolecular interactions with the MBr1 antibody.