Wang Hanxuan, Liu Zhichao, An Chuanjing, Li Haoting, Hu Fanlei, Dong Suwei
State Key Laboratory of Natural and Biomimetic Drugs and Department of Chemical Biology School of Pharmaceutical Sciences Peking University Beijing 100191 China.
Department of Rheumatology and Immunology Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing 100044 China.
Adv Sci (Weinh). 2020 Jul 2;7(16):2001264. doi: 10.1002/advs.202001264. eCollection 2020 Aug.
Polysaccharides are a class of carbohydrates that play pivotal roles in living systems such as being chemical messengers in many vital biological pathways. However, the complexity and heterogeneity of these natural structures have posed daunting challenges on their production, characterization, evaluation, and applications. While there have been various types of synthetic skeletons that could mimic some biological aspects of polysaccharides, a safer and more easily accessed system is still desired to avoid the unnatural components and difficulties in modifying the structures. In this work, conveniently accessible self-assembling glycopeptide conjugates are developed, where the natural O-glycosidic linkages and phosphoryl modifications assist the self-assembly and concurrently reduce the risk of toxicity. The generated nanoparticles in aqueous solution offer a multivalent display of structurally controllable carbohydrates as mimics of polysaccharides, among which a mannosylated version exhibits immunostimulatory effects in both cellular assays and vaccination of mice. The obtained results demonstrate the potential of this glycopeptide conjugate-derived platform in exploiting the intriguing properties of carbohydrates in a more structurally maneuverable fashion.
多糖是一类碳水化合物，在生命系统中发挥着关键作用，例如在许多重要的生物途径中作为化学信使。然而，这些天然结构的复杂性和异质性对其生产、表征、评估和应用提出了艰巨的挑战。虽然已经有各种类型的合成骨架可以模拟多糖的一些生物学特性，但仍需要一个更安全、更容易获得的系统，以避免非天然成分和结构修饰的困难。在这项工作中，开发了易于获得的自组装糖肽缀合物，其中天然的O-糖苷键和磷酸化修饰有助于自组装，同时降低毒性风险。在水溶液中生成的纳米颗粒提供了结构可控的碳水化合物的多价展示，作为多糖的模拟物，其中一种甘露糖基化形式在细胞试验和小鼠疫苗接种中均表现出免疫刺激作用。所得结果证明了这个源自糖肽缀合物的平台在以更具结构可操作性的方式利用碳水化合物的有趣特性方面的潜力。
