Synthesis of sulfated oligosaccharide glycosides having high anti-HIV activity and the relationship between activity and chemical structure.
Sulfated laminara-oligosaccharide glycosides having high anti-human immunodeficiency virus (HIV) activities were synthesized from laminara-tetraose, -pentaose and -hexaose. The oligosaccharide glycosides were synthesized by treating peracetylated beta-oligosaccharides with various alcohols and Lewis acid catalysts. The effects of the number of glucose residues and the alkyl chain-length on anti-HIV activity were examined. The anti-HIV activity of sulfated dodecyl laminara-pentaosides and -hexaosides increased with increasing degree of sulfation (DS) and the pentaoside having an almost fully-sulfated saccharide portion had the highest activity, whereas for the hexaoside a somewhat lower DS manifested the highest activity. Sulfated laminara-oligosaccharide glycosides having fluoroalkyl-containing aglycons of high hydrophobicity showed potent inhibitory effects against HIV infection. In contrast, hydrophilic substituents containing oligo(ethyleneoxy) groups as aglycons in the sulfated oligosaccharides did not show high anti-HIV activity.
Katsuraya
K
K
Institute of Industrial Science, University of Tokyo, Japan.
Nakashima
H
H
Yamamoto
N
N
Uryu
T
T
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D006027:Glycosides / Q000138:chemical synthesis*; D006801:Humans; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D006027:Glycosides; D009844:Oligosaccharides