Department of Chemistry, Pukyong National University, Busan 608-737, Republic of Korea.
Carbohydr Res. 2010 Mar 30;345(5):656-62. doi: 10.1016/j.carres.2009.12.017. Epub 2009 Dec 23.
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 (EC(50) 2.19 microg/ml), lytic effect (EC(50) 1.43 microg/ml), and p24 antigen production (EC(50) 4.33 microg/ml and 7.76 microg/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.
壳寡糖是通过壳聚糖的酶解得到的无毒水溶性化合物，壳聚糖是通过脱乙酰过程从几丁质中获得的。壳寡糖具有广泛的活性，如抗肿瘤、抗真菌、抗菌活性。不同分子量的硫酸化壳寡糖（SCOSs）通过随机硫酸化反应合成。在本研究中，研究了 SCOSs 的抗 HIV-1 特性及其分子量对其抑制活性的影响。发现 SCOS III（MW 3-5 kDa）是抑制 HIV-1 复制最有效的化合物。在非毒性浓度下，SCOS III 对 HIV-1 诱导的合胞体形成（EC（50）2.19 μg/ml）、裂解作用（EC（50）1.43 μg/ml）和 p24 抗原产生（EC（50）4.33 μg/ml 和 7.76 μg/ml，用于 HIV-1（RF）和 HIV-1（Ba-L））表现出显著的抑制活性。相比之下，未硫酸化的壳寡糖对 HIV-1 没有活性。此外，研究发现 SCOS III 通过破坏 HIV-1 gp120 与 CD4 细胞表面受体的结合，阻断病毒进入和病毒-细胞融合。这些结果表明，硫酸化壳寡糖是开发抗 HIV-1 药物的新型候选物。
