Multivalent neoglycoconjugates are valuable tools for studying
carbohydrate-
protein interactions. To study the interaction of HIV-1 gp120 with its reported alternate
glycolipid receptors,
galactosyl ceramide (GalCer) and
sulfatide,
galactose- and sulfated
galactose-derivatized
dendrimers were synthesized, analyzed as
ligands for rgp120 by surface plasmon resonance, and tested for their ability to inhibit HIV-1
infection of CXCR4- and CCR5-expressing
indicator cells. Four different series of glycodendrimers were made by
amine coupling spacer-arm derivatized
galactose residues, either sulfated or nonsulfated, to poly(propylenimine)
dendrimers, generations 1-5. One series of glycodendrimers was prepared from the
ceramide saccharide derivative of purified natural GalCer, and another was from chemically synthesized 3-(beta-D-galactopyranosylthio)propionic
acid. Synthesis of 3-sulfogalactopyranosyl-derivatized
dendrimers was accomplished using the novel compound, 3-(beta-D-3-sulfogalactopyranosylthio)propionic
acid. The fourth series was made by random sulfation of the 3-(beta-D-galactopyranosylthio)propionic
acid functionalized
dendrimers. Structures of the
carbohydrate moieties were confirmed by NMR, and the average molecular weights and polydispersities of the different glycodendrimers were determined using MALDI-TOF MS. Surface plasmon resonance studies found that rgp120 IIIB bound to the derivatized
dendrimers tested with nanomolar affinity, and to
dextran sulfate with picomolar affinity. In vitro studies of the effectiveness of these compounds at inhibiting
infection of U373-MAGI-CCR5 cells by HIV-1 Ba-L indicated that the sulfated glycodendrimers were better inhibitors than the nonsulfated glycodendrimers, but not as effective as
dextran sulfate.