Chemical Synthesis and Antigenic Evaluation of Inner Core Oligosaccharides from Acinetobacter baumannii Lipopolysaccharide.

Chemical Synthesis and Antigenic Evaluation of Inner Core Oligosaccharides from Acinetobacter baumannii Lipopolysaccharide.
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鲍曼不动杆菌脂多糖内核寡糖的化学合成和抗原评价。

DOI:
10.1002/anie.202204420
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发表时间:
2022
期刊:
影响因子:
--
通讯作者:
Jin‐Song Yang
Jin‐Song Yang
中科院分区:
--
文献类型:
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作者:
Xian;Lingxin Li;Zhen Zhang;S. Duan;Ying;Yi;Xiao;Zhi;Yong Qin;Jing Hu;Jian Yin;Jin‐Song Yang

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鲍曼不动杆菌目前对全球健康构成严重威胁。脂多糖(LPS)是革兰阴性菌的一种强毒力因子。探讨A.鲍曼不动杆菌LPS,来自A.合成了鲍曼不动杆菌菌株ATCC 17904。建立了一种基于正交取代α-Kdo-(2→5)-Kdo二糖的灵活多样的方法。选择性地去除这些关键前体中的不同保护基团,并通过与5,7- O -二叔丁基硅烯或5- O -苯甲酰基保护的Kdo硫代糖苷和2-叠氮基-2-脱氧葡萄糖基硫代糖苷的α-立体控制偶联延长糖链,使目标分子有效组装。对感染患者血清的聚糖微阵列分析表明,4,5-分支的Kdo三聚体是一个潜在的抗原表位,这对于进一步的免疫学研究开发抗A.鲍曼不动杆菌。
Acinetobacter baumannii  is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii  LPS, four Kdo-containing inner core glycans from A. baumannii  strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7- O -di- tert -butylsilylene or 5- O -benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against  A. baumannii.