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着重要而多样的作用，并且是治疗干预，临床诊断和潜在药物的目标。虽然已经为大多数生物分子设计了能够选择性地作为受体（或配体）的化合物，但很少有描述能够在水溶液中与简单碳水化合物进行高亲和力非共价结合的化合物。侦探他的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，这些化合物能在水中结合单糖和更复杂的脂糖，其亲和力比任何先前描述的合成受体强两到三个数量级。本文所描述的研究旨在利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。通过对三环戊烷碳水化合物受体的系统变化，研究了氢键、构象变异性、立体化学、疏水效应、CH-pi和阳离子-pi相互作用的相对贡献。其中一种化合物单独或与碳水化合物客体配合的核磁共振分析将提供有关结合相互作用的高分辨率结构信息。这项研究将为我们理解基本的糖生物学、设计以碳水化合物为目标的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).