Naoya Ikushima

Sulfated alkyl oligosaccharides with potent inhibitory effects on human immunodeficiency virus infection

Compounds with medium relative molecular masses active against human immunodeficiency virus (HIV) were synthesized. Sulfated alkyl oligosaccharides such as sulfated octadecyl maltohexaoside, sulfated dodecyl laminaripentaoside and sulfated dodecyl laminari-oligomer caused 50% inhibition of virus infection in the EC50 range of 0.4-0.7 microgram/mL in vitro using the MT-4 cell line and HIV-1HTLV-IIIB virus isolate, though sulfated oligosaccharides without alkyl groups showed low anti-HIV activities. This anti-HIV activity was close to the EC50 of 0.43 microgram/mL for a highly active sulfated polysaccharide curdlan sulfate which was reported to inhibit completely the HIV infection at a concentration as low as 3.3 micrograms/mL. These compounds were also active against HIV-2 and a clinically isolated HIV-1 with reduced AZT sensitivity. For such sulfated alkyl oligosaccharides, the mechanism of inhibition of HIV infection was assumed to be the inhibition of HIV binding to the cell and to some extent the interaction of the alkyl portion with the lipid bilayer of the virus.

Synthesis of sulfated alkyl malto- and laminara-oligosaccharides with potent inhibitory effects on AIDS virus infection

A series of sulfated alkyl oligosaccharides, including a sulfate dodecyl laminarapentaoside and a sulfated octadecyl maltohexaoside with potent anti-human immunodeficiency virus (HIV) activity, has been synthesized. An alkyl oligosaccharide in which a long alkyl group is bonded to the reducing end of the oligosaccharide was first synthesized in high yield. Peracetylated oligosaccharides reacted with such aliphatic alcohols as 1-decyl and 1-dodecyl alcohols with Lewis acids as catalysts. As in the glycosylation of the alpha and beta peracetylated glycosides, the beta anomer reacted exclusively, the acetylation was carried out with a sodium acetate-acetic anhydride at high temperatures to maximize the proportion of the beta anomer.