Chemical Functionalization and Polymerization of Peptide Particle Assemblies

University Of Delaware, Newark DE

Investigators

Abstract

With this award, the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry is funding Professors Christopher Kloxin and Darrin J. Pochan of the University of Delaware to design and synthesize synthetic polymers that replicate and ultimately complement some of the capabilities of naturally occurring bimoacromolecules. Biomacromolecules have precise sequences, are universal in nature, and have folded structures the perform numerous functions, from molecular recognition to catalysis. Within these complex structures, there are common reoccurring structural units such as alpha helices, beta sheets, coiled coils and loops upon which the overall protein structure is build. While nature uses folded substructures as a major design element, the majority of synthetic polymers lack such modular design and are less functionally sophisticated. To bridge this gap, this research designs and prepares complex polymers using short peptide sequences that assemble into robust and well defined coil-coil units called bundlemers. These sequences are rapidly produced using microwave-based methods and are then incorporated into long polymer chains. Computational modelling is used to design bundlemers. Structural features of assembled polymers, such as stability and physical properties, are also systematically investigated. Research activities provide undergraduate and graduate students with valuable educational experience in polymer and materials chemistry. The research team is further broadening the impact of their work by contributing to various outreach activities and programs that involve K-12 students and broader community. Additionally, a database of functional coiled-coils, analogous to the protein bank, is developed to provide new resources to researchers and educators. The research team is developing a new approach for designing and preparing complex polymeric nanostructures using short peptide sequences that assemble into robust and well defined coil-coil units called bundlemers. The research leverages concepts from computational design of biological assemblies for the de novo design of nonbiological nanomaterials with new crosslinking and functionalization capabilities. The project involves three distinct objectives. The first objective is to understand bundlemer functionalization and polymerization while the second is to synthesize bundlemer bottles brushes and stars using atom transfer radical polymerization (ATRP). The third objective is to introduce bundlemer stapling by stabilizing assembled polymeric structures utilizing crosslinking of amino acids with different peptide chains. Through these objectives, the conditions and constraints for the assembly of click-functionalized coiled-coil peptides to be implemented as a fundamental unit for polymer design and synthesis may be established. Additionally, the effect of non-biological residues and covalent linkages on coiled-coil formation and stability as well as on reactive group accessibility, localization, and confinement is investigated. Finally, stable supramolecular assembles with precise exterior displays of highly efficient click functional groups are created, providing routes to new macromolecular assembly pathways though physical (noncovalent) interactions and subsequent stabilization via covalent interactions. This new methodology for macromolecule fabrication has the potential to impact a wide range of research areas and applications, ranging from peptide-based therapeutics to catalysis. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.