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拟生物分子之间的相互作用来帮助揭示生命的过程。碳水化合物的结合特别神秘，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验证的水中常见单糖的受体。我们的设计可以比作一座经典的寺庙，在那里，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TAME)，旨在将二糖结合在(不太具挑战性的)有机介质中。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够与水中的双糖和低聚糖结合的受体--这是第一个专门为此目的而设计的分子。受体可能表现出很高的亲和力，也许可以与一些碳水化合物结合蛋白(凝集素)相媲美。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工作的介质。我们还将开发可应用于生物研究的版本。一个目标是利用受体的荧光类似物，在发育的细胞壁中突出目标双糖。另一种是干扰细胞壁的合成，可能会导致抗菌剂的出现。如果我们成功了，我们将第一次证明，仿生碳水化合物受体在生物学环境中是有用的。

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