三种常见高度耐药菌糖抗原的合成研究进展  

Research progress on the chemical synthesis of carbohydrate antigens from three highly drug-resistant bacteria

作　　者：邹小鹏 秦春君 田光宗 胡静 尹健 Xiaopeng Zou;Chunjun Qin;Guangzong Tian;Jing Hu;Jian Yin(Key Laboratory of Carbohydrate Chemistry and Biotechnology,Ministry of Education,School of Biotechnology,Jiangnan University,Wuxi 214122,China;Wuxi School of Medicine,Jiangnan University,Wuxi 214122,China;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：《科学通报》2024年第25期3785-3798,共14页Chinese Science Bulletin

基　　金：国家自然科学基金(22325803,22277042,22077052,22207042);江南大学糖化学与生物技术教育部重点实验室开放课题(KLCCB-KF202203)资助。

摘　　要：耐药菌感染每年导致全世界数百万人死亡,严重危及人类生命健康.随着耐药菌抗药性的增强,使用抗生素治疗耐药菌感染效果逐渐减弱,而疫苗接种是预防耐药菌感染的有效手段.细菌表面特异性多糖结构是糖蛋白结合疫苗开发的靶标分子,已上市的糖蛋白结合疫苗大幅降低了菌血症、脑膜炎以及肺炎等疾病的发生,保障了人类的生命健康.相比从细菌表面提取天然多糖制备糖蛋白结合疫苗,通过化学法合成结构明确、均一的寡/多糖抗原是新一代糖蛋白结合疫苗的发展方向.本文主要介绍了幽门螺旋杆菌、铜绿假单胞菌、鲍曼不动杆菌三种常见高度耐药菌表面复杂糖类抗原的合成研究进展.针对寡/多糖合成过程中区域选择性、立体选择性、反应活性调控和空间位阻等问题,国内外研究人员通过开发新的糖基化离去基团、正交保护基,优化反应条件,调整糖基化反应序列,高效地实现了一系列高度耐药菌表面复杂糖抗原结构的制备,为耐药菌糖蛋白结合疫苗的开发奠定了基础.Drug-resistant bacterial infections are significant global threats, resulting in millions of deaths annually and posing serious risks to human health. The emergence of antimicrobial resistance has the potential to result in consequences that are more severe than those seen with COVID-19 in the future. The growing resistance of bacteria weakens the effectiveness of antibiotics, making vaccination a crucial strategy to prevent infection caused by drug-resistant bacteria. Surface-exposed carbohydrates on pathogens are often immunogenic and are considered as potential candidates for carbohydrate-based vaccine development. Commercial glycoconjugate vaccines are currently being utilized for the prevention of diseases such as bacteremia, pneumonia, and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, resulting in the saving of millions of lives every year. Most of licenced glycoconjugate vaccines are constructed using polysaccharides isolated from bacterial surface in historically. Naturally isolated polysaccharides pose challenges due to their non-uniform components and mixed potential microbial contaminants, which limited the quality improvement of the glycoconjugate vaccines. Additionally, not all pathogens can be feasible to culture on a large scale.Chemical synthetic carbohydrate antigens with well-defined and high pure structures offer a desirable tool for identifying the best epitope and designing the next generation of glycoconjugate vaccines.This review highlights recent advancements in the chemical synthesis of complex carbohydrate antigens derived from the surfaces of three high drug-resistant bacteria. All three bacteria have been listed as antibiotic-resistant “priority pathogens”by World Health Organization in 2017, and currently, there are no vaccines against these bacterial infections. The discussion includes the synthesis of conserved core oligosaccharides and O antigens from H. pylori LPS, as well as the synthesis of Psl exopolysaccharide fra

关 键 词：耐药菌 幽门螺旋杆菌 铜绿假单胞菌 鲍曼不动杆菌 糖抗原 化学合成 

分 类 号：TQ460.6[化学工程—制药化工]