Department of Agricultural Bio-Resources, National Academy of Agricultural Science, RDA, Suwon, South Korea.
Glycoconj J. 2011 Aug;28(6):411-8. doi: 10.1007/s10719-011-9340-7. Epub 2011 Jul 9.
We investigated the inhibitory activity of glycosaminoglycans (GAGs) in terms of growth, adhesion, and VacA vacuolation of Helicobacter pylori. Intact acharan sulfate (AS, MW:114 kDa) potently inhibited H. pylori adhesion to Kato III cells with IC(50) value of 1.4 mg/mL, while other GAGs did not show any inhibitory activity except for heparin which is a well-known inhibitor of H. pylori adhesion. To investigate whether low molecular weight acharan sulfate (LMWAS) can inhibit H. pylori adhesion, we performed chemical depolymerization of AS by radical reactions to obtain LMWAS. Its physicochemical properties were characterized by high-performance size exclusion chromatography (HPSEC), agarose gel electrophoresis, disaccharide compositional analysis after digestion with heparinase II, and (1)H-NMR spectroscopy. The most potent molecular size of LMWAS was 3 kDa with IC(50) value of 32 μg/mL, which is 44-fold more potent than intact AS. These results suggest that AS as well as other GAGs can be chemically depolymerized by free radicals and LMWAS compared to intact AS can be applied as a pharmaceutical candidate in order to inhibit H. pylori adhesion to Kato III cells.
我们研究了糖胺聚糖(GAGs)在生长、黏附和空泡毒素 VacA 空泡形成方面对幽门螺杆菌的抑制活性。完整的硫酸乙酰肝素(AS,MW:114 kDa)可强烈抑制幽门螺杆菌与 Kato III 细胞的黏附,IC50 值为 1.4 mg/mL,而其他 GAG 除了肝素外均没有表现出任何抑制活性,肝素是一种众所周知的幽门螺杆菌黏附抑制剂。为了研究低分子量硫酸乙酰肝素(LMWAS)是否可以抑制幽门螺杆菌的黏附,我们通过自由基反应对 AS 进行化学解聚,得到 LMWAS。通过高效体积排阻色谱法(HPSEC)、琼脂糖凝胶电泳、肝素酶 II 消化后的二糖组成分析以及(1)H-NMR 光谱对其理化性质进行了表征。LMWAS 的最有效分子大小为 3 kDa,IC50 值为 32 μg/mL,比完整的 AS 强 44 倍。这些结果表明,与完整的 AS 相比,AS 以及其他 GAG 可以通过自由基化学解聚,而 LMWAS 可以作为一种抑制幽门螺杆菌与 Kato III 细胞黏附的药物候选物。