幽门螺杆菌脂多糖抗原表位片段的化学合成及抗体亲和力研究  

Chemical synthesis and antibody affinity of epitope fragments from Helicobacter pylori lipopolysaccharide

作　　者：赵慧 邹小鹏 肖蕾 胡静 尹健 ZHAO Hui;ZOU Xiaopeng;XIAO Lei;HU Jing;YIN Jian(Key Laboratory of Carbohydrate Chemistry and Biotechnology(Ministry of Education),School of Biotechnology,Jiangnan University,Wuxi 214122;Wuxi School of Medicine,Jiangnan University,Wuxi 214122;School of Life Sciences and Health Engineering,Jiangnan University,Wuxi 214122,China)

机构地区：[1]江南大学生物工程学院糖化学与生物技术教育部重点实验室,无锡214122 [2]江南大学无锡医学院,无锡214122 [3]江南大学生命科学与健康工程学院,无锡214122

出　　处：《中国药科大学学报》2024年第5期645-656,共12页Journal of China Pharmaceutical University

基　　金：国家自然科学基金项目(No.22207042,No.22177041,No.22277042,No.22325803);江南大学糖化学与生物技术教育部重点实验室开放课题(No.KLCCB-KF202203)。

摘　　要：幽门螺杆菌(Helicobacter pylori, Hp)是引发慢性胃炎、消化性溃疡,甚至胃癌的重要致病菌,目前尚无上市预防或治疗Hp感染的疫苗。本研究通过化学法合成了Hp脂多糖核心寡糖中不同链长的α-1,6-葡聚糖片段(二糖至六糖),使用基于酰基远程参与作用和溶剂效应的协同糖基化策略成功构建了1,2-顺式-糖苷键。糖芯片筛选结果显示,脂多糖免疫兔血清和患者血清中的IgG抗体均能与合成的α-1,6-葡聚糖片段结合;脂多糖免疫兔血清IgG抗体与α-1,6-葡聚三糖具有较强的结合能力;绝大多数Hp感染患者血清IgG抗体能够很好地识别α-1,6-葡聚三糖和五糖,部分患者血清IgG抗体与α-1,6-葡聚二糖具有较强的结合作用。此研究结果表明,α-1,6-葡聚二糖、三糖和五糖可能是Hp脂多糖中的重要糖抗原片段。Helicobacter pylori(Hp)is responsible for chronic gastritis,peptic ulcers,and even gastric cancers.Currently,there is no vaccine to prevent or treat Hp infections.Here,we described the chemical synthesis ofα-1,6-glucans with different lengths(di-to hexasaccharide),which are present in the core oligosaccharide of Hp lipopolysaccharide(LPS).The 1,2-cis-glucosidic bonds were constructed successfully using a synergistic glycosylation strategy based on acyl remote participation and solvent effects.The results of glycan microarrays indicated that all synthesizedα-1,6-glucan fragments possessed a strong binding to IgG antibodies in both rabbit serum immunized with Hp O1 LPS and patient serum infected with Hp.Theα-1,6-linked trisaccharide exhibited strong binding affinity to anti-LPS rabbit IgG antibodies.Theα-1,6-glucan trisaccharide and pentasaccharide elicited a strong response to IgG antibodies in sera of most Hp-infected patients.Some patients’sera exhibited strong binding activity withα-1,6-linked disaccharide.The results suggest that theα-1,6-glucan disaccharide,trisaccharide and pentasaccharide could be important carbohydrate antigen fragments in Hp lipopolysaccharide.

关 键 词：幽门螺杆菌 脂多糖 α-1 6-葡聚糖 糖芯片 抗体亲和力 

分 类 号：O629.1[理学—有机化学] R914[理学—化学]