School of Chemistry, University of Bristol, Bristol, UK.
Org Biomol Chem. 2011 May 21;9(10):3598-610. doi: 10.1039/c0ob01017k. Epub 2011 Mar 16.
The multitude of roles that carbohydrates and their glyco-conjugates play in biological processes has stimulated great interest in determining the nature of their interactions in both normal and diseased states. Manipulating such interactions will provide leads for drug discovery. Of the major classes of biomolecule, carbohydrates are the most structurally diverse. This hetereogeneity makes isolation of pure samples, and in sufficient amounts, from biological sources extremely difficult. Chemical synthesis offers the advantage of producing pure and structurally defined oligosaccharides for biological investigations. Although the complex nature of carbohydrates means that this is challenging, recent advances in the field have facilitated access to these molecules. The synthesis and isolation of oligosaccharides combined with progress in glycoarray technology have aided the identification of new carbohydrate-binding drug targets. This review aims to provide an overview of the latest advancements in carbohydrate chemistry and the role of these complex molecules in drug discovery, focusing particularly on synthetic methodologies, glycosaminoglycans, glycoprotein synthesis and vaccine development over the last few years.
碳水化合物及其糖缀合物在生物过程中扮演的众多角色激发了人们极大的兴趣,促使人们去研究在正常和疾病状态下它们相互作用的本质。操纵这些相互作用将为药物发现提供线索。在主要的生物分子类别中,碳水化合物的结构多样性最大。这种异质性使得从生物来源中分离出纯样品并获得足够数量的样品变得极其困难。化学合成具有生产用于生物学研究的纯的和结构确定的寡糖的优势。尽管碳水化合物的复杂性质意味着这具有挑战性,但该领域的最新进展已经为获得这些分子提供了便利。寡糖的合成和分离以及糖基阵列技术的进步促进了新的碳水化合物结合药物靶标的鉴定。这篇综述旨在概述碳水化合物化学的最新进展,以及这些复杂分子在药物发现中的作用,重点关注过去几年中在合成方法学、糖胺聚糖、糖蛋白合成和疫苗开发方面的进展。