Sulfated oligosaccharide cluster with polylysine core scaffold as a new anti-HIV dendrimer
Sulfated oligosaccharide cluster with polylysine core scaffold as a new anti-HIV dendrimer
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DOI：
10.1016/j.carbpol.2010.01.031
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发表时间：
2010-05-16
影响因子：
11.2
通讯作者：
Yoshida, Takashi
中科院分区：
文献类型：
--
作者：
Han, Shuqin;Yoshida, Dai;Yoshida, Takashi
以纤维二糖和第三代多聚赖氨酸树枝状大分子为原料，制备了多聚赖氨酸树枝状纤维二糖硫酸酯，合成了多聚赖氨酸树枝状硫酸纤维二糖4。硫酸化程度为1.85/葡萄糖单位（最大3）。通过GPC测量的分子量为（M）/bar（w）= 12.4 × 10（3）和（M）/bar（n）= 10.4 × 10（3），表明硫酸化的4具有非常紧凑的结构。用KIT法在体外测定了聚赖氨酸-树枝状硫酸化纤维二糖4的抗HIV活性，表明对于病毒复制的50%抑制浓度，EC 50 = 3.2 μ g/ml，该浓度与目前临床使用的AIDS药物ddC的浓度一样高（EC_（50）= 3.51 μ g/ml）和低细胞毒性（CC_（50）= 1000 μ g/ml）。用美国药典方法测定的抗凝血活性AA = 19.4单位/mg，与硫酸化多糖硫酸葡聚糖（AA = 22.9单位/mg）和硫酸可得兰（AA = 19单位/mg）的抗凝血活性相同。这些结果表明，由于硫酸化低聚糖几乎没有抗HIV活性，因此源自树枝状结构的硫酸化纤维二糖的簇效应提高了生物活性。用核磁共振和红外光谱分析了聚赖氨酸树枝状硫酸纤维二糖4的结构。(C)2010爱思唯尔有限公司版权所有。
Polylysine-dendritic sulfated cellobiose 4 was synthesized by sulfation of polylysine-dendritic cellobiose, which was prepared from cellobiose and polylysine dendrimer generation 3. The degree of sulfation was 1.85 per glucose unit (maximum 3). The molecular weights measured by GPC were (M) over bar (w) = 12.4 x 10(3) and (M) over bar (n) = 10.4 x 10(3), suggesting that the sulfated 4 had a very compact structure. The anti-HIV activity of polylysine-dendritic sulfated cellobiose 4 was assayed in vitro by the KIT method, which indicated that the EC50 = 3.2 mu g/ml for the 50% inhibitory concentration of virus replication, a concentration that is as high as that of the currently clinical used AIDS drug, ddC (EC50 = 3.51 mu g/ml), and low cytotoxicity (CC50 = 1000 mu g/ml). The blood anticoagulant activity determined by the method of the United States Pharmacopoeia was AA = 19.4 unit/mg, as the same as that of the sulfated polysaccharides, dextran sulfate (AA = 22.9 unit/mg) and curdlan sulfate (AA = 19 unit/mg). These results suggest that the biological activities were improved by a cluster effect of the sulfated cellobiose that originated from the dendritic structure because sulfated oligosaccharides have little anti-HIV activity. The structure of polylysine-dendritic sulfated cellobiose 4 was analyzed by NMR and FT-IR measurements. (C) 2010 Elsevier Ltd. All rights reserved.