Chemistry Seminar with Dr. Jai Rudra from WashU Biomedical Engineering at 4:00pm

Self-assembling peptides serve as adaptable platforms for creating nanostructured biomaterials, and their assembly outcomes are highly sensitive to primary sequence, stereochemistry, and side-chain modifications. We synthesize and compare design motifs to elucidate how factors such as chirality, co-assembly, and substituent effects influence molecular packing and supramolecular morphologies. Our findings demonstrate that selectively substituting d-amino acids into amphipathic repeats can significantly alter assembly across multiple hierarchical levels. Coassembly experiments show that matching N-terminal chirality promotes coassembly, whereas mismatched chirality leads to self-sorting behavior, highlighting the importance of stereochemical arrangement in multicomponent systems. Additionally, the electronic properties of substituents on aromatic side chains affect assembly and immunogenicity. Para-substituted benzyl groups and variations in linker length between the backbone and aromatic moieties strongly influence fibril formation, molecular packing, and immune responses both in vitro and in vivo, providing practical strategies to modify peptide nanomaterials for vaccine delivery, tissue engineering, and regenerative medicine.