Synthetic Lectins for Oligosaccharide Binding in Aqueous Media

用于水介质中寡糖结合的合成凝集素

• 批准号: EP/D060192/1
• 负责人: Anthony Davis
• 金额: $ 29.55万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FD060192%2F1
• 关键词: Synthetic; Lectins; Oligosaccharide; Binding; Aqueous

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.

合成受体可以通过模仿生物分子之间的相互作用来帮助揭示生命过程。碳水化合物的结合尤其神秘，并且在自然（水）条件下尤其难以复制。我们最近展示了第一个经过充分验证的水中常见单糖受体。我们的设计可以比作一座古典寺庙，其中屋顶、地板和柱子与碳水化合物的匹配部分接触。我们还研究了一种更长的类似物（扩展寺庙），旨在在（挑战性较小的）有机介质中结合二糖。后一种化合物仅对一种二糖底物表现出非凡的选择性。我们现在计划制造能够结合水中的二糖和寡糖的受体——第一个专门为此目的而设计的分子。这些受体可能表现出高亲和力，可能与某些碳水化合物结合蛋白（凝集素）相当。它们还应对植物、真菌和细菌细胞壁中发现的特定二糖单元表现出良好的选择性。我们将利用它们来研究天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行的​​介质。我们还将开发可应用于生物学研究的版本。目的之一是利用受体的荧光类似物来突出发育细胞壁中的目标二糖。另一种是中断细胞壁合成，可能会产生抗菌剂。如果我们成功，我们将首次证明仿生碳水化合物受体可以在生物学背景下发挥作用。

项目成果

Desymmetrisation of Biphenyl-Based Carbohydrate Receptors: A Nonbonding Pillar in One Corner of the Cage

联苯类碳水化合物受体的去对称化：笼子一角的非键合支柱

• DOI: 10.1055/s-2008-1078020
• 发表时间: 2008
• 期刊: Synlett
• 影响因子: 2
• 作者: Davis A

A synthetic lectin for O-linked beta-N-acetylglucosamine.

• DOI: 10.1002/anie.200804905
• 发表时间: 2009
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Ferrand, Yann;Klein, Emmanuel;Barwell, Nicholas P.;Crump, Matthew P.;Jimenez-Barbero, Jesus;Vicent, Cristina;Boons, Geert-Jan;Ingale, Sampat;Davis, Anthony P.
• 通讯作者: Davis, Anthony P.

Synthesis of Regioselectively Functionalized Pyrenes via Transition-Metal-Catalyzed Electrocyclization

通过过渡金属催化电环化合成区域选择性功能化芘

• DOI: 10.1055/s-0030-1258238
• 发表时间: 2010
• 期刊: Synthesis
• 作者: Davis A