Review
Anti-HIV Mechanism of Sulfated Poly and Oligosaccharides
2020 年 76 巻 12 号 p. 387-402
詳細
2020 年 76 巻 12 号 p. 387-402
This review focuses on the previous and recent results as well as related literatures regarding the anti-HIV mechanism of sulfated alkyl poly- and oligosaccharides.
.To clarify the anti-HIV mechanism of sulfated polysaccharides, curdlan sulfate was mainly used because of having potent anti-HIV activity and low cytotoxicity. Curdlan sulfate was prepared by sulfation of a natural occurring polysaccharide curdlan bearing linear (1→3)-β-D-glucopyranosidic structure. Nuclear magnetic resonance (NMR) analysis of the mixture of curdlan sulfate and an oligopeptide from the C-terminus of HIV envelope (surface) glycoprotein gp120 (HIV gp120) suggested that the anti-HIV activity of curdlan sulfate depended on electrostatic interactions between negatively charged sulfate groups in sulfated polysaccharides and positively charged amino acids in HIV gp120. The mechanism was assumed to be similar to the electrostatic interaction between a natural blood anticoagulant sulfated polysaccharide heparin and a protease inhibitor antithrombin III. In addition, the anti-HIV mechanism of curdlan sulfate was quantitatively investigated using surface plasmon resonance (SPR) and dynamic light scattering (DLS) measured with oligopeptides from three regions in HIV gp120, V3 loop, C-terminus, and CD4 binding domain. These studies revealed the interaction between oligopeptides of the V3 loop and C-terminus bearing positively charged amino acid accumulated regions in each sequence. These results indicated that the anti-HIV activity of sulfated polysaccharides involves electrostatic interactions.
It was reported that a long-chain alkyl group in sulfated alkyl oligosaccharides plays a key role in the enhancement of anti-HIV activity. The interaction between sulfated alkyl poly- and oligosaccharides and liposomes as a model of HIV was also discussed by SPR and DLS measurements, suggesting that the long-chain alkyl group penetrated into the lipid bilayer of HIV, and then sulfated poly- and oligosaccharide portions electrostatically interacted with HIV gp120 to produce potent anti-HIV activity.
