The Self-Assembly of Peptide-Dendron Hybrids

肽-Dendron杂化物的自组装

• 批准号: 0750004
• 负责人: Jon Parquette
• 金额: $ 43.2万
• 依托单位: Ohio State University Research Foundation -DO NOT USE
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0750004&HistoricalAwards=false
• 关键词: Self; Assembly; Peptide; Dendron; Hybrids

With the support of this award from the Organic and Macromolecular Chemistry Program, Professor Jon Parquette of the Ohio State University will investigate peptide superstructures which are ubiquitous in the natural world and have shown tremendous potential for future biomedical applications. However, the availability of synthetic superstructures based on oligopeptides is still limited. This research will attempt to determine how the coupled conformational equilibria of peptides and dendrons within chimeric structures impact their propensity to assemble into higher-order structures. Attempts will be made to delineate the structural factors that determine the stability of higher-order peptide-dendron (PD) assemblies so that this knowledge can ultimately be used to reversibly control their structure and/or trigger their formation and destruction. Strategies to modulate the assembly of higher-order structures will not only be critical for the creation of "smart" electronic, optical, or bio-materials, but will also contribute to the knowledge-base that enables the development of therapies to reverse the beta-sheet self-assembly process leading to amyloid-based diseases such as Alzheimer's, Parkinson's, systemic amyloidosis, and type II diabetes. It is proposed to achieve this level of structural control by studying the properties of supramolecular assemblies composed of multiple structural elements, each of which exhibits unique and well-defined conformational equilibria. Broader Impacts: Emerging technologies such as nano- and biotechnology, and materials chemistry are necessarily interdisciplinary in nature and many new career opportunities for chemists are materializing in these new technologies. The interdisciplinary nature of the work described in this proposal will teach students a variety of skills associated with the design and synthesis of supramolecular structures and will expose them to a broad range of computational and spectroscopic techniques. The development of methods to modulate the assembly of higher-order structures also has important biomedical and materials implications. A controllable self-assembly process will drive the creation of "smart" materials with extrinsically tunable physical, optical or electronic properties. Furthermore, the fundamental knowledge obtained in this work about the mechanism and dynamics of peptide aggregation will enable the development of molecular strategies to reverse the beta-sheet self-assembly processes leading to amyloid-based disease.

在有机和高分子化学项目的支持下，俄亥俄州州立大学的Jon Parquette教授将研究自然界中普遍存在的肽超结构，并在未来的生物医学应用中显示出巨大的潜力。然而，基于寡肽的合成超结构的可用性仍然有限。 这项研究将试图确定如何耦合的构象平衡的肽和树突内嵌合结构的影响他们的倾向，组装成更高的顺序结构。 将尝试描绘的结构因素，确定高阶肽-树突（PD）组件的稳定性，使这方面的知识可以最终被用来可逆地控制它们的结构和/或触发它们的形成和破坏。调节高阶结构组装的策略不仅对于创建“智能”电子，光学或生物材料至关重要，而且还将有助于开发能够逆转β-折叠自组装过程的疗法的知识基础，从而导致淀粉样蛋白疾病，如阿尔茨海默氏症，帕金森氏症，系统性淀粉样变性和II型糖尿病。建议通过研究由多个结构元素组成的超分子组装体的性质来实现这种水平的结构控制，每个结构元素都具有独特的和明确定义的构象平衡。更广泛的影响：纳米和生物技术以及材料化学等新兴技术本质上必然是跨学科的，这些新技术为化学家带来了许多新的职业机会。 本提案中描述的工作的跨学科性质将教会学生与超分子结构的设计和合成相关的各种技能，并将使他们接触到广泛的计算和光谱技术。 调制高阶结构组装方法的发展也具有重要的生物医学和材料意义。 一个可控的自组装过程将推动创造“智能”材料，具有额外的可调物理，光学或电子性能。此外，在这项工作中获得的关于肽聚集的机制和动力学的基础知识将使分子策略的发展能够逆转导致淀粉样蛋白疾病的β-折叠自组装过程。