School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.
Chem Soc Rev. 2013 Jun 7;42(11):4613-22. doi: 10.1039/c2cs35430f. Epub 2012 Dec 21.
Protein toxins released by certain intestinal bacteria are the cause of many diarrhoeal diseases including cholera and travellers' diarrhoea. The toxins enter their target cells by first binding to specific glycolipids in the cell membrane. Inhibition of these protein-carbohydrate interactions has the potential to prevent the toxins from reaching their site of action, and thus avoid the ensuing diarrhoea. Simple oligosaccharides typically have low affinities for the protein toxins, therefore inhibitor design has focussed on exploiting the principles of multivalency: multiple weak interactions acting in concert can enhance the overall binding interaction. The major classes of multivalent inhibitors investigated to date will be discussed; these include glycopolymers, glycodendrimers, tailored glycoclusters and inhibitors exploiting templated assembly.
某些肠道细菌释放的蛋白毒素是许多腹泻病的病因，包括霍乱和旅行者腹泻。这些毒素首先通过与细胞膜上的特定糖脂结合进入靶细胞。抑制这些蛋白-碳水化合物相互作用有可能阻止毒素到达其作用部位，从而避免随之而来的腹泻。简单的寡糖通常对蛋白毒素的亲和力较低，因此抑制剂的设计集中在利用多价性原则上：多个弱相互作用协同作用可以增强整体结合相互作用。迄今为止，已讨论了主要的多价抑制剂类别；这些包括糖聚合物、糖树状聚合物、定制糖簇和利用模板组装的抑制剂。
