MOLECULAR RECOGNITION IN BIOMIMETIC RECEPTORS

仿生受体中的分子识别

• 批准号: 2177796
• 负责人: ANDREW D HAMILTON
• 金额: $ 17.17万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2177796
• 关键词: aminoacid biosynthesis; carboxylate; catalyst; chemical binding; chemical models; chemical structure function; chemical synthesis; chromatography; cis trans isomerization; hydrogen bond; hydroxyl group; inositol phosphates; ionic bond; molecular site; nuclear magnetic resonance spectroscopy; phosphoric ester; receptor; sialate; solvents

This proposal describes development of artificial receptors for the selective complexation of biologically significant molecules and the design of new biomimetic catalysts based on transition state stabilization. Our approach will exploit combined hydrogen bonding, electrostatic and hydrophobic interactions to maintain strong binding in organic and aqueous solvent. Detailed analysis of the structure as well as thermodynamic and kinetic properties of these systems will lead to increased understanding of intermolecular interactions in a range of solvent environments. In designing receptors that are complementary to postulated transition state structures we hope not only to develop new biomimetic catalysts but also to probe, with a precision not possible in the natural system, details of the reaction mechanism of the catalysts. An important application of the receptors will be in the construction of molecule-selective sensors. Our specific aims include the design, synthesis and evaluation of artificial receptors for the key second messenger, inositol 1,4,5- trisphosphate. We will use a tris-guanidinium binding site and will investigate the relative importance of solvophobic effects and pi- stacking orientations in binding. A similar approach will be taken to the recognition of other key carbohydrates including sialic acid and inositol. As part of this work we will investigate polyphosphodiesters as a novel class of water soluble, hydrogen bonding receptors. A second major area will be the development of synthetic receptors as catalysts based on the selective recognition and stabilization of key transition state structures. We will focus on several reactions including the rearrangement of chorismate to prephenate. We will prepare a family of chorismate receptors capable of binding to different conformations of the diacid along the reaction pathway. Analysis of the kinetic effects of the hosts will allow us to determine the optimal binding arrangement for stabilizing the transition state. Electrostatic groups will also be incorporated into the receptor potentially to assess their role in the catalytic mechanism. This strategy will also be applied to other reactions including the Claisen and Cope rearrangements and the cis-trans isomerization of amide bonds.

该提案描述了用于该疾病的人工受体的开发。 选择性络合生物学上重要的分子， 基于过渡态的新型仿生催化剂设计 稳定化 我们的方法将利用结合氢键， 静电和疏水相互作用，以保持强结合， 有机溶剂和水溶剂。 结构的详细分析 因为这些系统的热力学和动力学性质将导致 增加了对一系列分子间相互作用的理解， 溶剂环境。 在设计受体时， 假设的过渡态结构，我们不仅希望开发新的 仿生催化剂，也可以探测，精确度不可能在 自然体系，催化剂的反应机理的细节。 受体的一个重要应用将是构建 分子选择性传感器 我们的具体目标包括设计，合成和评估 关键第二信使肌醇1，4，5-的人工受体 三磷酸盐 我们将使用三胍结合位点， 研究疏溶剂效应和π的相对重要性， 装订中的堆叠方向。 将采取类似的办法， 其他关键碳水化合物的识别，包括唾液酸和 肌醇。 作为这项工作的一部分，我们将研究聚磷酸二酯 作为一类新的水溶性氢键受体。 第二 主要领域将是作为催化剂的合成受体的开发 基于关键转换的选择性识别和稳定 国家结构。 我们将重点讨论几种反应，包括 分支酸盐重排为预苯酸盐。 我们将准备一个家庭， 分支酸受体能够结合不同构象的 二酸沿着反应途径。 动力学效应分析 主机将允许我们确定最佳绑定安排， 稳定过渡状态。 静电组也将 潜在地结合到受体中以评估它们在 催化机理 这一战略也将适用于其他 包括Claisen和科普重排以及顺-反重排的反应 酰胺键的异构化。