Synthesis and Characterization of Coiled-coil Bundlemer Peptide-based Networks

• Kameron Hall, Chemistry, Virginia Polytechnic Institute and State University

• Xinqiao Jia, Materials Science and Engineering, University of Delaware

Recent advances in peptide synthesis have led to the development of a new class of peptide-based polymers known as bundlemers. These computationally designed, self-assembling homotetrameric coiled-coil peptides exhibit hierarchical α-helical architectures that provide a versatile platform for studying peptide-based polymer assembly. This work investigates the polymerization behavior of the DK-F3 bundlemer variant, with an emphasis on how linker length influences polymer architecture. DK-F3 incorporates three VPGFG amino acid flexible linker units that increase the distance between reactive groups and promote intermolecular connectivity. Polymerization was driven through an inverse electron-demand Diels-Alder reaction between tetrazine and trans-cyclooctene (TCO) functionalized DK-F3 bundlemers. The extended linker length favored intermolecular crosslinking over linear polymerization, resulting in the formation of a crosslinked gel network. These findings demonstrate that increasing linker length is an effective strategy for directing bundlemer assembly into three-dimensional polymer networks and provide new insight into the relationship between peptide architecture and polymerization behavior in self-assembling peptide systems.