MOLECULAR RECOGNITION OF CARBOHYDRATES IN SOLUTION

描述(由申请人提供)：碳水化合物在细胞中扮演着重要的和不同的角色，是治疗干预、临床诊断和潜在药物的目标。虽然能够选择性地作为受体(或配体)的化合物被设计用于大多数生物分子，但很少有人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的化合物。P.I.S实验室最近开发了一系列基于高度取代的四环戊烷的化合物，它们与水中的单糖和更复杂的脂糖结合在一起，亲和力比之前描述的任何合成受体都要紧密两到三个数量级。这里描述的研究试图使用这些受体和类似的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，将考察氢键、构象可变性、立体化学、疏水效应、CH-pi和阳离子-pi相互作用的相对贡献。单独对其中一种化合物和与碳水化合物客体络合的核磁共振分析将提供关于结合作用的高分辨率结构信息。这项研究将提供对我们理解基础糖生物学至关重要的见解，对于我们设计碳水化合物靶向药物的能力，以及对诊断设备(生物传感器)的开发至关重要。

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).