Sulfated oligosaccharide cluster with polylysine core scaffold as a new anti-HIV dendrimer

Polylysine-dendritic sulfated cellobiose 4 was synthesized by sulfation of polylysine-dendritic cellobiose, which was prepared from cellobiose and polylysine dendrimer generation 3. The degree of sulfation was 1.85 per glucose unit (maximum 3). The molecular weights measured by GPC were M ¯ w = 12.4 × 10 3 and M ¯ n = 10.4 × 10 3 , suggesting that the sulfated 4 had a very compact structure. The anti-HIV activity of polylysine-dendritic sulfated cellobiose 4 was assayed in vitro by the MTT method, which indicated that the EC50 = 3.2 μg/ml for the 50% inhibitory concentration of virus replication, a concentration that is as high as that of the currently clinical used AIDS drug, ddC (EC50 = 3.51 μg/ml), and low cytotoxicity (CC50 = 1000 μg/ml). The blood anticoagulant activity determined by the method of the United States Pharmacopoeia was AA = 19.4 unit/mg, as the same as that of the sulfated polysaccharides, dextran sulfate (AA = 22.9 unit/mg) and curdlan sulfate (AA = 19 unit/mg). These results suggest that the biological activities were improved by a cluster effect of the sulfated cellobiose that originated from the dendritic structure because sulfated oligosaccharides have little anti-HIV activity. The structure of polylysine-dendritic sulfated cellobiose 4 was analyzed by NMR and FT-IR measurements.