Evidence indicates that
galactosyl ceramide (GalCer) and its 3'-sulfated derivative,
sulfatide (SGalCer), may act as alternate coreceptors for human immunodeficiency virus type 1 (HIV-1) in CD4(-) cells.
Glycosphingolipids (GSLs) may also be necessary for fusion of HIV-1 and host cell membranes. Using an
enzyme-linked
immunosorbent assay to determine which GSL was the best
ligand for both recombinant and virus-associated gp120, we found that SGalCer was the best
ligand for each rgp120 and HIV-1 isolate tested. Therefore, novel multivalent glycodendrimers, which mimic the
carbohydrate clustering reportedly found in
lipid rafts, were synthesized based on the
carbohydrate moiety of SGalCer. Here we describe the synthesis of a polysulfated
galactose functionalized, fifth generation DAB
dendrimer (PS Gal 64mer), containing on average two
sulfate groups per
galactose residue. Its ability to inhibit HIV-1
infection of cultured
indicator cells was compared to that of
dextran sulfate (DxS), a known, potent, binding inhibitor of HIV-1. The results indicate that the PS Gal 64mer inhibited
infection by the HIV-1 isolates tested as well as DxS.