| We have synthesized and investigated the Pk-trisaccharide and its deoxy analogs as inhibitors of cell surface adhesion processes. The common alpha-Galp-(1→4)-beta-Galp epitope of the natural globoseries saccharides is the receptor site of the Shiga toxins. We conducted chemical mapping studies of P k trisaccharide-Shiga toxin Type 1 interactions using 7 deoxy analogs of Pk-trisaccharide. Synthesis of the 2', 3', 6', 2", 3", 4" and 6"-monodeoxy analogs of methyl globotrioside was performed using a variety of deoxygenation methods.;FTICR-MS was used to evaluate the binding affinity of the Pk-trisaccharide and its deoxy analogs. The 3"-deoxy trisaccharide 24 showed the lowest affinity of all ligands tested. Surprisingly, the 6"-deoxy trisaccharide 26 was found to exhibit similar binding affinity to the native ligand despite a crystallographically documented involvement of 6"-OH in hydrogen bonding with the protein in all 3 putative binding sites. |
