Synthetic Lectins for Oligosaccharide Binding in Aqueous Media

合成受体可以通过模拟生物分子之间的相互作用来帮助阐明生命的过程。碳水化合物的结合是特别神秘的，在自然（水）条件下特别难以复制。我们最近展示了第一个经过验证的受体，用于水中常见的单糖。我们的设计可以比作一座古典寺庙，屋顶、地板和柱子与碳水化合物的匹配部分联系在一起。我们还研究了一种较长的类似物（扩展-temple），设计用于在有机介质中结合双糖（挑战性较小）。后一种化合物仅对一种双糖底物表现出非凡的选择性。我们现在计划制造能在水中结合双糖和寡糖的受体，这是第一个专门为此目的设计的分子。受体可能表现出高亲和力，可能与一些碳水化合物结合蛋白（凝集素）相当。它们还应该对植物、真菌和细菌细胞壁中发现的特定双糖单位表现出良好的选择性。我们将使用它们来研究自然碳水化合物结合的驱动力，例如通过改变它们的结构和它们运作的介质。我们还将开发可应用于生物学研究的版本。一个目的是利用受体的荧光类似物来突出发展细胞壁的目标双糖。另一种是中断细胞壁的合成，可能导致抗菌剂的产生。如果我们成功了，我们将首次证明，仿生碳水化合物受体在生物环境中是有用的。

Synthetic receptors can help to throw light on the processes of life by mimicking the interactions between biomolecules. The binding of carbohydrates is especially mysterious, and especially difficult to reproduce under natural (aqueous) conditions. We have recently demonstrated the first well-authenticated receptor for the common monosaccharides in water. Our design may be likened to a classical temple, in which roof, floor and pillars make contact with matching portions of the carbohydrate. We have also studied a longer analogue ( extended-temple ) designed to bind disaccharides in (less challenging) organic media. This latter compound shows extraordinary selectivity for just one disaccharide substrate.We now plan to make receptors which will bind di- and oligosaccharides in water - the first molecules to be specifically designed for this purpose. The receptors are likely to show high affinities, perhaps comparable with some carbohydrate-binding proteins (lectins). They should also show good selectivities for particular disaccharide units which are found in plant, fungal and bacterial cell walls. We will use them to study the driving forces for natural carbohydrate binding, for example by varying their structures and the medium in which they operate. We will also develop versions which can be applied in biological research. One aim is to highlight the target disaccharides in developing cell walls, using fluorescent analogues of the receptors. Another is to interrupt cell wall synthesis, perhaps leading to antimicrobial agents. If we succeed we will have demonstrated, for the first time, that biomimetic carbohydrate receptors can be useful in a biological context.