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) over bar (w) = 12.4 x 10(3) and (M) over bar (n) = 10.4 x 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 KIT method, which indicated that the EC50 = 3.2 mu g/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 mu g/ml), and low cytotoxicity (CC50 = 1000 mu g/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. (C) 2010 Elsevier Ltd. All rights reserved.