Capsular Assemblies Driven by the Hydrophobic Effect

由疏水效应驱动的胶囊组件

• 批准号: 7032211
• 负责人: BRUCE C GIBB
• 金额: $ 24.5万
• 依托单位: UNIVERSITY OF NEW ORLEANS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032211
• 关键词: antimalarial agents; calorimetry; chemical kinetics; chemical stability; chemical synthesis; combinatorial chemistry; dimer; dosage forms; drug delivery systems; drug discovery /isolation; fluorescence spectrometry; hydropathy; microcapsule; molecular assembly /self assembly; molecular dynamics; nuclear magnetic resonance spectroscopy; phenols; protein structure function; solubility; water solution

DESCRIPTION (provided by applicant): Project Summary The long-term objectives of this proposal are: 1) to learn how molecular structure and the hydrophobic effect combine to promote the assembly of nano-capsules in aqueous solution; 2) to use this information to both gain an understanding of quaternary protein structure, and devise self-assembling nano-capsules that function as drug delivery systems. The aim of this proposal is the synthesis and analysis of water-soluble cavitands that assemble into nano-scale capsules, and in doing so entrap guest molecules within their hollow interiors. Four cavitands that differ in cavity shape and size, and the area of hydrophobic surface that promotes assembly, will be synthesized. Each can be "coated" with an external layer of functionality that modulates their assembly properties. In combination these variables engenders hundreds of homo- and hetero-capsules. Capsule formation will be examined as a function of guest to determine how they influence assembly. In addition, we will examine how the capsules kinetically stabilize normally reactive compounds. Of particular interest in this regard will be the analysis of potential anti-malarial drugs that are too unstable or insoluble to individually demonstrate activity. Analysis of the systems will be carried out with Nuclear Magnetic Resonance (NMR) spectroscopy, Isothermal Titration Calorimetry (ITC), and fluorescence spectroscopy. Relevance The development of new drug delivery systems allows new avenues for attacking disease states. In mimicry of Nature's most efficient drug delivery systems - viruses - this proposal outlines investigations into the formation and properties of nano-capsules. To date, little is known about how nano-capsules assemble in water. Hence, these studies will provide valuable information pertaining to this novel field of research.

描述（由申请人提供）： 项目概要 该提案的长期目标是：1）了解分子结构和疏水效应如何结合以促进纳米胶囊在水溶液中的组装； 2）利用这些信息来了解四级蛋白质结构，并设计出充当药物输送系统的自组装纳米胶囊。 该提案的目的是合成和分析组装成纳米级胶囊的水溶性空配体，并在此过程中将客体分子捕获在其中空内部。将合成四个空腔形状和大小以及促进组装的疏水表面面积不同的空配体。每个部件都可以“涂覆”一层功能性外层，以调节其装配特性。这些变量结合起来产生了数百个同质和异质胶囊。将检查胶囊的形成作为客体的功能，以确定它们如何影响组装。此外，我们将研究胶囊如何在动力学上稳定通常反应性的化合物。在这方面特别令人感兴趣的是对潜在的抗疟疾药物的分析，这些药物太不稳定或不溶而无法单独证明其活性。系统分析将通过核磁共振（NMR）光谱、等温滴定量热法（ITC）和荧光光谱进行。 关联 新药物输送系统的开发为攻击疾病状态提供了新途径。该提案模仿了自然界最有效的药物输送系统——病毒——概述了对纳米胶囊的形成和特性的研究。迄今为止，人们对纳米胶囊如何在水中组装知之甚少。因此，这些研究将为这一新的研究领域提供有价值的信息。