The Self-Assembly of Peptide-Dendron Hybrids

Ohio State University Research Foundation -Do Not Use, Columbus OH

Investigators

Abstract

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.