MOLECULAR RECOGNITION OF CARBOHYDRATES IN SOLUTION

描述（由申请人提供）：碳水化合物在细胞中发挥重要和不同的作用，并且作为治疗干预、临床诊断的靶点和作为潜在的药物是令人感兴趣的。虽然已经为大多数生物分子设计了能够选择性地用作受体（或配体）的化合物，但是很少有描述能够与水溶液中的简单碳水化合物高亲和力非共价结合。私家侦探实验室最近开发了一系列基于高度取代的三环戊烷的化合物，这些化合物在水中与单糖和更复杂的脂糖结合，其亲和力比以前描述的任何合成受体都高出两到三个数量级。本文描述的研究试图使用这些受体和类似分子来详细了解碳水化合物结合的结构因素。通过系统的变化tercyclopentane碳水化合物受体，氢键，构象变化，立体化学，疏水效应，CH-π，阳离子-π相互作用的相对贡献将被检查。这些化合物之一的NMR分析单独和复杂的碳水化合物客人将提供高分辨率的结合相互作用的结构信息。这项研究将为我们理解基础糖生物学，设计碳水化合物靶向药物制剂以及开发诊断设备（生物传感器）提供至关重要的见解。

DESCRIPTION (provided by applicant): Carbohydrates play important and varied roles in the cell, and are of interest as targets for therapeutic intervention, clinical diagnosis, and as potential pharmaceuticals. While compounds capable of selectively serving as receptors (or ligands) have been designed for most biological molecules, very few have been described that are capable of high-affinity noncovalent binding to simple carbohydrates in aqueous solution. The P.I.'s laboratory has recently developed a series of compounds, based on highly substituted tercyclopentanes, that bind simple sugars and more complex liposaccharides in water with affinities two to three orders of magnitude tighter than any previously described synthetic receptors. The research described herein seeks to use these receptors, and analogous molecules, to develop a detailed understanding of the structural factors underlying carbohydrate binding. Through systematic variation of tercyclopentane carbohydrate receptors, the relative contributions of hydrogen bonding, conformational variability, stereochemistry, hydrophobic effects, CH-pi, and cation-pi interactions will be examined. NMR analyses of one of these compounds alone and complexed with carbohydrate guests will provide high-resolution structural information about the binding interactions. This research will provide insights vital to our understanding of fundamental glycobiology, to our ability to design carbohydrate-targeted pharmaceutical agents, and to the development of diagnostic devices (biosensors).