Novel polysulfated galactose-derivatized dendrimers as binding antagonists of human immunodeficiency virus type 1 infection.
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.
Kensinger
Richard D
RD
Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Catalone
Bradley J
BJ
Krebs
Fred C
FC
Wigdahl
Brian
B
Schengrund
Cara-Lynne
CL
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016264:Dextran Sulfate / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005697:Galactosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects; D011073:Polyamines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013433:Sulfoglycosphingolipids / Q000494:pharmacology
D019380:Anti-HIV Agents; D005697:Galactosides; D011073:Polyamines; D013433:Sulfoglycosphingolipids; D016264:Dextran Sulfate