Capsular Assemblies Driven by the Hydrophobic Effect

描述（由申请人提供）： 项目摘要 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联合收割机以促进纳米胶囊在水溶液中的组装; 2）使用这些信息来获得对四级蛋白质结构的理解，并设计作为药物递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穴，并在其中空内部捕获客体分子。将合成四种不同的空腔形状和大小以及促进组装的疏水表面面积的空腔。每一个都可以用调节其组装特性的功能性外层“涂覆”。这些变量结合在一起产生了数百个同性和异性胶囊。胶囊的形成将作为客体的函数进行检查，以确定它们如何影响组装。此外，我们将研究如何胶囊动力学稳定正常反应的化合物。在这方面，特别感兴趣的是分析潜在的抗疟疾药物，这些药物太不稳定或不溶性，无法单独证明活性。将采用核磁共振（NMR）光谱、等温滴定量热法（ITC）和荧光光谱对系统进行分析。 相关性 新的药物输送系统的发展为攻击疾病状态提供了新的途径。在模仿自然界最有效的药物输送系统-病毒-这一建议概述了纳米胶囊的形成和性质的调查。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。

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.