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.

项目总结