Kushwaha Divya, Xu Peng, Kováč Pavol
NIDDK, LBC, National Institutes of Health, Bethesda, MD 20892-0815 (U.S.A.).
RSC Adv. 2017;7(13):7591-7603. doi: 10.1039/C6RA27181B. Epub 2017 Jan 24.
Synthetic multivalent glycoclusters that carry carbohydrate antigen epitopes have been recognized as promising candidates for the development of carbohydrate based vaccines. Here we describe a convergent strategy for the synthesis of conjugation-ready multivalent glycoclusters using sugars as versatile core subcarriers. d-Glucose and gentiobiose were converted into poly-alkyne functionalized cores which were then decorated with an azide bearing model ligand d-glucose using click chemistry, to form structurally well-defined tetra- and heptavalent glycoclusters. Each cluster was conjugated to a model protein bovine serum albumin (BSA) by squaric acid chemistry. Carbohydrate clusters can be prepared in a variety of sizes and spatial arrangements by altering the structure and configuration of the core, depending on the mono-, or oligosaccharides used for their assembly. It is suggested that the use of carbohydrate as core subcarriers provides an opportunity to tailor the size and topology of antigens and modify multivalent presentation of immunogens in a way to optimize cluster effect for stronger immunoreactivity.
携带碳水化合物抗原表位的合成多价糖簇已被认为是基于碳水化合物的疫苗开发的有前途的候选物。在此,我们描述了一种以糖作为通用核心载体合成可用于偶联的多价糖簇的汇聚策略。将d-葡萄糖和龙胆二糖转化为多炔官能化的核心,然后使用点击化学用带有叠氮化物的模型配体d-葡萄糖进行修饰,以形成结构明确的四价和七价糖簇。通过方酸化学将每个簇与模型蛋白牛血清白蛋白(BSA)偶联。通过改变核心的结构和构型,可以根据用于组装的单糖或寡糖制备各种尺寸和空间排列的碳水化合物簇。有人提出,使用碳水化合物作为核心载体提供了一个机会,可以调整抗原的大小和拓扑结构,并以优化簇效应以增强免疫反应性的方式改变免疫原的多价呈现。