Total Synthesis of a Pentasaccharide O‐Glycan from Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a Gram-negative bacteria associated with drug resistance and infection in healthcare settings. An understanding of both the biological roles and antigenicity of surface molecules of this organism may provide an important step in the prevention and treatment of infection through vaccination or the development of monoclonal antibodies. With this in mind, we have performed the multistep synthesis of a conjugation-ready pentasaccharide O-glycan from A. baumannii with a longest linear synthetic sequence of 19 steps. This target is particularly relevant due to its role in both fitness and virulence across an apparently broad range of clinically relevant strains. Synthetic challenges include formulating an effective protecting group strategy as well as the installation of a particularly difficult glycosidic linkage between the anomeric position of a 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid and the 4-position of D-galactose.

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

“…2022 年，Seeberger 课题组 [73] 和 Ragains 课题组 [74] 四糖片段是鲍曼不动杆菌 17978 型关键的抗原表位 [73] 。 2023 年，孙建松课题组 [67] 报道了鲍曼不动杆菌 SMAL 型荚膜多糖四糖片段 124 的合成(图 [76] 报道了鲍 [77,78] 糖繁琐冗长的合成路线是限制合成糖疫苗规模化制备的主要因素。 借助计算机对糖基供体与受体 活性、空间构型的预测，合理优化合成路线，越来越受到寡/多糖合成设计的青睐 [88] 。糖科学经 历了几十年的发展，糖合成技术也取得了许多重大突破。以 Seeberger 课题组 [89] 和叶新山课题组 [90] 为代表的固相和液相自动合成仪的发展极大地缩短寡多糖的制备时间，提高了复杂糖链合成 效率，为合成糖蛋白结合疫苗的产业化奠定了基础。近年来糖生物技术的发展促进了酶在细菌表 面糖抗原的合成中的应用，化学法和酶法的结合使用，已逐渐成为获取细菌表面特异性糖抗原的 重要手段 [91,92] 。 我们相信，随着合成技术、免疫学及结构生物学的不断发展进步，更多有效的糖抗原将被合 成并应用于新一代耐药菌糖蛋白结合疫苗的开发，造福于人类的健康。 参考文献 Research progress on the chemical synthesis of carbohydrate antigens from three highly drug-resistant bacteria Xiaopeng Zou 1 , Chunjun Qin 1 , Guangzong Tian 1 , Jing Hu 2 , Jian Yin 1,3 The match and mismatch between the glycosyl donor and acceptor were addressed by a judicious choice of electron-withdrawing or electron-donating protecting group. The construction of the 1,2-cis-glycosidic bonds were accomplished through the utilization of the remote participation effect, the steric hindrance effect or the ring conformation locking effect of the protecting group.…”

Total Synthesis of Conjugation-Ready Tetrasaccharide Repeating Units of a Multidrug-Resistant Pathogen Acinetobacter baumannii Strain 34 and O5

“…For this purpose, chemically pure and structurally well characterized synthetic epitopes with a functionalized linker for protein attachment are required. There are a few reports in literature on chemical synthesis of other Acinetobacter baumannii strains. − Herein, we report the first total synthesis of conjugation-ready tetrasaccharide repeating units of Acinetobacter baumannii strain 34 ( 1a ) and O5 ( 1b ) (Scheme ).…”