Chemical synthesis and immunological evaluation of Helicobacter pylori serotype O6 tridecasaccharide O-antigen containing a DD-heptoglycan
Chemical synthesis and immunological evaluation of Helicobacter pylori serotype O6 tridecasaccharide O-antigen containing a DD-heptoglycan
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含DD-庚聚糖的幽门螺杆菌血清型O6十三糖O-抗原的化学合成及免疫学评价
DOI：
10.1002/anie.202004267
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Yin Jian
中科院分区：
文献类型：
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作者：
Tian Guangzong;Hu Jing;Qin Chunjun;Li Lingxin;Zou Xiaopeng;Cai Juntao;Seeberger Peter H.;Yin Jian
幽门螺杆菌糖结合疫苗的开发具有挑战性。一个H的确切表位。含有Lewis决定簇低聚糖和独特的d-七聚糖的幽门螺杆菌多糖(LPS)O-抗原尚未被鉴定。本文报道了H的首次全合成。幽门螺杆菌O6型十三糖O-抗原通过[(2×1)+(3+8)]组装序列，含有末端莱四糖、独特的α-(1→3)-、α-(1→6)-和α-(1→2)连接的七聚糖以及β-d-半乳糖连接体。制备了覆盖整个O-抗原不同部分的7种寡糖，用于免疫学研究，重点是阐明dd-七聚糖和莱特糖的作用。对分离的O6型脂多糖免疫的兔血清进行的糖链芯片分析显示，α-(1→3)连接的七聚糖具有体液免疫应答，这是设计糖结合疫苗的关键基序。幽门螺杆菌O6型。
The development of glycoconjugate vaccines againstHelicobacter pyloriis challenging. An exact epitope of theH. pylorilipo‐polysaccharide (LPS) O‐antigens that contain Lewis determinant oligosaccharides and uniquedd‐heptoglycans has not yet been identified. Reported here is the first total synthesis ofH. pyloriserotype O6 tridecasaccharide O‐antigen containing a terminal Leytetrasaccharide, a unique α‐(1→3)‐, α‐(1→6)‐, and α‐(1→2)‐linked heptoglycan, and a β‐d‐galactose connector, by an [(2×1)+(3+8)] assembly sequence. Seven oligosaccharides covering different portions of the entire O‐antigen were prepared for immunological investigations with a particular focus on elucidation of the roles of thedd‐heptoglycan and Leytetrasaccharide. Glycan microarray analysis of sera from rabbits immunized with isolated serotype O6 LPS revealed a humoral immune response to the α‐(1→3)‐linked heptoglycan, a key motif for designing glycoconjugate vaccines forH. pyloriserotype O6.