Molecular Design in l-Glutamic Acid-Based Peptide Assembly Dynamics Driven by Carbodiimide-Fueled Reaction Cycle

Molecular self-assembly creates complex structures through noncovalent interactions. Synthetic fuel-driven systems mimic biology, yet the effects of subtle design changes, particularly hydrophobic groups such as alkyl chains, are still not well understood. This study showed that the alkyl chain length critically influences the dynamic assembly of short peptides. Z-capped peptides C3 and C6, composed of l-phenylalanine and -glutamic acid, with L-aspartic acid as the reactive site and alkylamide groups of varying lengths at the C-terminus, have been observed to form metastable aggregates via intramolecular anhydride formation during a chemically fueled reaction cycle. We elucidated that the difference in alkyl chain length resulted in either highly dynamic assemblies or delayed structural dissolution. Our findings provide a comprehensive understanding of these observations, illustrating how rational peptide design enable precise control over nanostructure properties and catalytic lifetimes.