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

The synthesis of the trisacchatide alpha-L-Fucp-(1-->2)-beta-D-Galp-(1-->3)-beta-D-Galp (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 H-1-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. (C) 1999 Elsevier Science Ltd. All rights reserved.