Synthesis of Polymeric AIDS Dryg with Lasting Activity

核呋喃、木呋喃和葡聚糖硫酸酯等人工合成的多糖不仅表现出较高的抗艾滋病病毒(HIV)活性，而且具有较高的抗凝血活性，这被认为是副作用。本研究首次合成了具有较高抗HIV活性但较低抗凝血活性的硫酸酯多糖。以1，3-β-β-连接的抗癌多糖香菇多糖为原料，用哌啶N-磺酸进行磺化反应，得到了香菇多糖硫酸酯。香菇多糖硫酸酯具有较高的抗HIV活性，在体外可完全抑制艾滋病病毒对T淋巴细胞的感染，其浓度为3.3µg/ml。此外，它还表现出较低的抗凝血活性，约为20U/mg。然后，将与香菇多糖具有相同主链结构的细菌多糖可得胶用相同的方法进行硫酸盐化，得到可德聚糖硫酸酯。柯德兰硫酸盐具有较高的抗HIV活性，在3.3ug/ml浓度下对病毒感染有抑制作用，而在15U/mg浓度下表现出较低的抗凝活性。将硫酸可得聚糖引入动物血液中，进入肝、肾、淋巴结和骨髓等组织，注射后60-180分钟内从血液中消失。将L-葡萄糖、L-甘露糖等非天然糖类与可得糖、合成核呋喃反应，形成L糖基支链，使硫酸可得胶长时间保持在较高水平。对于L-糖基支链多糖硫酸酯，体内抗凝活性在血液中的保留时间为几个小时。结果表明，被吸收的硫酸可德聚糖在组织中存在几十天，没有发生主链降解。合成的1，6-α-D-甘露聚糖硫酸酯具有较高的抗HIV活性和中等的抗凝血活性。

Such synthetic polysaccharides as ribofuranan, xylofuranan, and dextran sulfates showed not only high anti-AIDS virus (anti-HIV) activity, but also high anticoagulant activity which is assumed to be side effects. In this study, sulfated polysaccharides with high anti-HIV activity but low anticoagulant activity were for the first time synthesized. A 1, 3-beta-linked antitumor polysaccharide lentinan was sulfated with piperidine N-sulfonic acid to afford lentinan sulfate. Lentinan sulfate had high anti-HIV activity inhibiting completely AIDS virus infection to T lymphocytes in a concentration as low as 3.3 mug/ml in vitro. Moreover, it showed low anticoagulant activity of about 20 unit/mg. Next, a bacterial polysaccharide curdlan having the same backbone structure as lentinan was sulfated by the same method to give curdlan sulfate. Curdlan sulfate had a high anti-HIV activity which inhibits the virus infection in a a 3.3 mug/ml concentration, and showed low anticoagulant activity of 15 unit/mg. The curdlan sulfate introduced into animal blood was transported into such tissues as liver, kidney, lymph node, and bone marrow, disappearing from the blood in 60-180 minutes after injection. To keep the concentration of curdlan sulfate in blood in a high level for longer time, such nonnatural sugars as L-glucose and L-mannose were reacted with curdlan and syntheric ribofuranan to form L-glycosyl branchings. For L-glyscosyl-branched polysaccharide sulfates, in vivo retention time of the anticoagulant activity in blood was a few hours. It was revealed that the absorbed curdlan sulfate exisis in the tissue for a few ten days without being subjected to main chain degradation. Syntheric 1, 6-alpha-D-mannan sulfate had high anti-HIV activity and medium anticoagulant activity.