Synthesis, modeling and binding affinity of an ester analogue of the terminal trisaccharide of the tumor-associated antigen globo-H-1

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 a id of molecular mechanics energy minimizations, molecular dynamics simulati ons, and H-1-NMR spectroscopic analysis and resulted in strict analogy with those of 2. Nevertheless, analysis of MBr1 binding to these compounds indi cate that substitution of the acetamido group at C-2 with the eater group l owers the affinity, thus suggesting that the amide hydrogen atom of 2 is in volved in intermolecular interactions with the MBr1 antibody. (C) 1999 Else vier Science Ltd. All rights reserved.