Capsular Assemblies Driven by the Hydrophobic Effect

由疏水效应驱动的胶囊组件

• 批准号: 7575601
• 负责人: BRUCE C GIBB
• 金额: $ 18.55万
• 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/7575601
• 关键词: Antimalarials; Area; Binding; Biological; Calorimetry; Capsid; Cell Membrane Structures; Complex; Cyclodextrins; Development; Devices; Disease; Drug Delivery Systems; Encapsulated; Enzymes; Event; Family; Fluorescence Spectroscopy; Glean; Goals; Homo; Housing; Hydrophobic Surfaces; Investigation; Learning; Liposomes; Molecular; Molecular Structure; NMR Spectroscopy; Nature; Nuclear Magnetic Resonance; Pharmaceutical Preparations; Property; Protein Subunits; Proteins; Quaternary Protein Structure; Research; Research Personnel; Series; Shapes; Solubility; Solutions; Structure; Surface; System; Systems Analysis; Titrations; Tobacco Mosaic Virus; Viral; Virus; Water; analog; aqueous; capsule; drug candidate; improved; interest; mimicry; multicatalytic endopeptidase complex; nano; nanoassembly; nanoscale; novel; polypeptide; programs; self assembly; viral RNA

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.

项目摘要 该提案的长期目标是：1）了解分子结构和疏水如何 效应结合起来促进水溶液中纳米胶囊的组装； 2）将此信息用于 两者都可以了解第四纪蛋白结构，并设计自组装的纳米胶囊 充当药物输送系统。 该提案的目的是综合和分析水溶性的仓库 纳米尺度胶囊，并这样做将客人分子置于其空心内部。四个cavitands 这在腔形状和大小上有所不同，促进组装的疏水表面面积将是 合成。每个都可以用外部功能层“涂覆”，以调节其组装 特性。这些变量结合起来产生了数百个同型和异质胶囊。胶囊 形成将作为客人的函数检查，以确定他们如何影响组装。此外， 我们将检查胶囊如何运动稳定正常反应性化合物。特别感兴趣 在这方面，将分析潜在的抗疟疾药物，这些药物过于不稳定或不溶于 单独展示活动。对系统的分析将使用核磁 共振（NMR）光谱，等温滴定量热法（ITC）和荧光光谱。 关联 新药物输送系统的开发允许攻击疾病状态的新途径。在 模仿自然最有效的药物输送系统 - 病毒 - 该提案概述了调查 进入纳米胶囊的形成和特性。迄今为止，对纳米胶囊的了解知之甚少 在水中组装。因此，这些研究将提供与这个新颖领域有关的有价值的信息 研究。