Capsular Assemblies Driven by the Hydrophobic Effect

项目摘要 这项建议的长期目标是：1）了解分子结构和疏水性 影响联合收割机以促进纳米胶囊在水溶液中的组装; 2）使用该信息 都获得了对四级蛋白质结构的理解，并设计了自组装纳米胶囊， 作为药物输送系统。 本提案的目的是合成和分析水溶性空穴， 纳米尺度的胶囊，并在这样做时将客体分子捕获在其中空的内部。四穴 在空腔形状和尺寸以及促进组装的疏水表面的面积方面不同， 合成了每一个都可以被一个调节它们组装的功能性外层“包裹” 特性.这些变量结合在一起产生了数百个同性和异性胶囊。胶囊 形成将作为客体的函数来检查，以确定它们如何影响组装。此外，本发明还提供了一种方法， 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。特别感兴趣的 在这方面，将分析潜在的抗疟疾药物，这些药物太不稳定或不溶性， 单独展示活动。系统分析将采用核磁共振成像技术进行。 共振（NMR）光谱、等温滴定量热法（ITC）和荧光光谱。 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-这一建议概述了调查 纳米胶囊的形成和性质。迄今为止，人们对纳米胶囊如何 在水中集合。因此，这些研究将提供有关这一新领域的有价值的信息。 research.

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.