Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Lihu Avenue 1800, Wuxi, Jiangsu Province, 214122, P. R. China.
Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476, Potsdam, Germany.
Angew Chem Int Ed Engl. 2020 Aug 3;59(32):13362-13370. doi: 10.1002/anie.202004267. Epub 2020 May 27.
The development of glycoconjugate vaccines against Helicobacter pylori is challenging. An exact epitope of the H. pylori lipo-polysaccharide (LPS) O-antigens that contain Lewis determinant oligosaccharides and unique dd-heptoglycans has not yet been identified. Reported here is the first total synthesis of H. pylori serotype O6 tridecasaccharide O-antigen containing a terminal Le tetrasaccharide, 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 the dd-heptoglycan and Le tetrasaccharide. 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 for H. pylori serotype O6.
针对幽门螺杆菌的糖缀合物疫苗的开发具有挑战性。尚未确定含有刘易斯决定簇寡糖和独特 dd-庚糖的幽门螺杆菌脂多糖（LPS）O-抗原的确切表位。本文首次通过（2×1）+（3+8））组装序列，全合成了含有末端 Le 四糖、独特的α-（1→3）-、α-（1→6）-和α-（1→2）-连接的庚糖以及β-d-半乳糖连接器的幽门螺杆菌血清型 O6 十三糖 O-抗原。为了进行免疫学研究，制备了涵盖整个 O-抗原不同部分的七个寡糖，特别关注 dd-庚糖和 Le 四糖的作用。用分离的血清型 O6 LPS 免疫的兔子的糖基微阵列分析显示，针对α-（1→3）-连接的庚糖产生了体液免疫反应，这是设计用于治疗幽门螺杆菌血清型 O6 的糖缀合物疫苗的关键基序。
