Synthetic galactomannans with potent anti-HIV activity

Ring-opening polymerization of a new 1,6-anhydro disaccharide monomer, 1, 6-anhydro-2, 3-di-O-benzyl-4-O-(2′, 3′, 4′, 6′-tetra-O-benzyl-α-d-galactopyranosyl)-α-d-mannopyranose, was carried out using PF5 as a catalyst under high vacuum at −60 °C to give galactose branched mannopyranan (synthetic galactomannan), 4-O-α-d-galactopyranosyl-(1 → 6)-α-d-mannopyranan, after debenzylation with Na in liquid NH3. The ring-opening copolymerization with 1, 6-anhydro-tri-O-benzyl-α-d-mannopyranose in various feeds was also performed to give synthetic galactomannans with various proportions of galactose branches. After sulfation, sulfated synthetic galactomannans were found to have anti-HIV activity and cytotoxicity as high and low as those of standard curdlan and dextran sulfates, respectively, which are potent anti-HIV sulfated polysaccharides with low cytotoxicity. The anti-HIV mechanism of sulfated synthetic galactomannans used by poly-l-lysine as a model peptide of the HIV surface protein was estimated by using SPR, DSL, and zeta potential measurements, revealing the electrostatic interaction between negatively charged sulfate groups and positively charged amino groups.