Anti-HIV-1 activity of low molecular weight sulfated chitooligosaccharides
Anti-HIV-1 activity of low molecular weight sulfated chitooligosaccharides
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DOI：
10.1016/j.carres.2009.12.017
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发表时间：
2010-03-30
影响因子：
3.1
通讯作者：
Kim, Se-Kwon
中科院分区：
文献类型：
--
作者：
Artan, Murat;Karadeniz, Fatih;Kim, Se-Kwon
壳寡糖是通过酶降解壳聚糖而获得的无毒水溶性化合物，壳聚糖是通过脱乙酰化过程从甲壳素中衍生出来的。壳寡糖具有广泛的活性，例如抗肿瘤、抗真菌、抗菌活性。通过随机硫酸化反应合成了不同分子量的硫酸化壳寡糖（SCOS）。在本研究中，研究了 SCOS 的抗 HIV-1 特性以及分子量对其抑制活性的影响。 SCOS III（分子量 3-5 kDa）被发现是抑制 HIV-1 复制最有效的化合物。在无毒浓度下，SCOS III 对 HIV-1 诱导的合胞体形成（EC50 2.19 μg/ml）、裂解作用（EC50 1.43 μg/ml）和 p24 抗原产生（HIV-1（RF）和 HIV-1（Ba-L）的 EC50 分别为 4.33 μg/ml 和 7.76 μg/ml）表现出显着的抑制活性。相比之下，未硫酸化的壳寡糖没有表现出抗 HIV-1 的活性。此外，发现 SCOS III 可能通过破坏 HIV-1 gp120 与 CD4 细胞表面受体的结合来阻止病毒进入和病毒与细胞融合。这些结果表明，硫酸化壳寡糖代表了开发抗 HIV-1 药物的新候选物。 (C) 2009 Elsevier Ltd. 保留所有权利。
Chitooligosaccharides are nontoxic and water-soluble compounds obtained by enzymatic degradation of chitosan, which is derived from chitin by a deacetylation process. Chitooligosaccharides possess broad range of activities such as antitumour, antifungal, antibacterial activities. Sulfated chitooligosaccharides (SCOSs) with different molecular weights were synthesized by a random sulfation reaction. In the present study, anti-HIV-1 properties of SCOSs and the impact of molecular weight on their inhibitory activity were investigated. SCOS III (MW 3-5 kDa) was found to be the most effective compound to inhibit HIV-1 replication. At nontoxic concentrations, SCOS III exhibited remarkable inhibitory activities on HIV-1-induced syncytia formation (EC50 2.19 mu g/ml), lytic effect (EC50 1.43 mu g/ml), and p24 antigen production (EC50 4.33 mu g/ml and 7.76 mu g/ml for HIV-1(RF) and HIV-1(Ba-L), respectively). In contrast, unsulfated chitooligosaccharides showed no activity against HIV-1. Furthermore, it was found that SCOS III blocked viral entry and virus-cell fusion probably via disrupting the binding of HIV-1 gp120 to CD4 cell surface receptor. These results suggest that sulfated chitooligosaccharides represent novel candidates for the development of anti-HIV-1 agent. (C) 2009 Elsevier Ltd. All rights reserved.