The Self-Assembly of Peptide-Dendron Hybrids

在有机化学和高分子化学项目的支持下，俄亥俄州立大学的乔恩·帕奎特教授将研究自然界中普遍存在的多肽超结构，并显示出未来生物医学应用的巨大潜力。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嵌合结构中多肽和树突的耦合构象平衡如何影响它们组装成高阶结构的倾向。将试图描绘决定更高阶肽-树突(PD)组件稳定性的结构因素，以便这些知识最终可用于可逆地控制它们的结构和/或触发它们的形成和破坏。调控高阶结构组装的策略不仅对创造“智能”的电子、光学或生物材料至关重要，而且还将有助于知识库的开发，使治疗方法的开发能够逆转导致阿尔茨海默氏症、帕金森氏症、系统性淀粉样变性和II型糖尿病等淀粉样蛋白疾病的β-折叠自组装过程。为了实现这种水平的结构控制，人们建议通过研究由多个结构元素组成的超分子组件的性质来实现这一水平的结构控制，每个结构元素都表现出唯一和明确定义的构象平衡。更广泛的影响：新兴技术，如纳米和生物技术，以及材料化学，在性质上必然是跨学科的，化学家的许多新职业机会正在这些新技术中实现。这项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，并使他们接触到广泛的计算和光谱技术。调控高阶结构组装的方法的发展也具有重要的生物医学和材料意义。一种可控的自组装过程将推动具有外部可调物理、光学或电学特性的“智能”材料的创造。此外，在这项工作中获得的关于多肽聚集的机制和动力学的基础知识将使分子策略的发展成为可能，以逆转导致淀粉样蛋白疾病的β-折叠自组装过程。

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.