Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces Am Mühlenberg 1, 14476 Potsdam, Germany.
Institute of Chemistry and Biochemistry, Free University of Berlin, Arnimallee 22, 14195 Berlin, Germany.
Chem Rev. 2021 Apr 14;121(7):3598-3626. doi: 10.1021/acs.chemrev.0c01210. Epub 2021 Apr 1.
The glycocalyx, a thick layer of carbohydrates, surrounds the cell wall of most bacterial and parasitic pathogens. Recognition of these unique glycans by the human immune system results in destruction of the invaders. To elicit a protective immune response, polysaccharides either isolated from the bacterial cell surface or conjugated with a carrier protein, for T-cell help, are administered. Conjugate vaccines based on isolated carbohydrates currently protect millions of people against , type b, and infections. Active pharmaceutical ingredients (APIs) are increasingly discovered by medicinal chemistry and synthetic in origin, rather than isolated from natural sources. Converting vaccines from biologicals to pharmaceuticals requires a fundamental understanding of how the human immune system recognizes carbohydrates and could now be realized. To illustrate the chemistry-based approach to vaccine discovery, I summarize efforts focusing on synthetic glycan-based medicinal chemistry to understand the mammalian antiglycan immune response and define glycan epitopes for novel synthetic glycoconjugate vaccines against , , , and other bacteria. The chemical tools described here help us gain fundamental insights into how the human system recognizes carbohydrates and drive the discovery of carbohydrate vaccines.
糖萼是一层厚厚的碳水化合物，围绕着大多数细菌和寄生虫病原体的细胞壁。人体免疫系统识别这些独特的聚糖，导致入侵者被破坏。为了引发保护性免疫反应，多糖要么从细菌表面分离出来，要么与载体蛋白结合，以获得 T 细胞的帮助。基于分离的碳水化合物的结合疫苗目前可保护数百万人免受 A、B 和 C 型流感嗜血杆菌感染。越来越多的活性药物成分 (API) 是通过药物化学发现的，并且源自合成，而不是从天然来源中分离出来的。将疫苗从生物制品转化为药物需要对人体免疫系统如何识别碳水化合物有一个基本的了解，而这一目标现在已经可以实现。为了说明基于化学的疫苗发现方法，我总结了专注于合成糖基药物化学的努力，以了解哺乳动物抗糖免疫反应，并确定针对、、和其他细菌的新型合成糖缀合物疫苗的糖表位。这里描述的化学工具帮助我们深入了解人体系统如何识别碳水化合物，并推动碳水化合物疫苗的发现。
