Stepwise chemical control in the formation of beta-peptide assemblies

Peptidic foldamers are an important class of synthetic macromolecules and have gained high attention in different areas of nanotechnology, drug delivery and molecular biology.Small manipulations in peptide sequences: length, charge or amino acid chirality can lead to the formation of different morphological assemblies.We have recently demonstrated 1,2 that acyclic, lysine-rich, short beta-peptides can achieve nanostructures that closely mimic both the oligomerization and the filament formation of natural peptides.Here, we show how systematic small variations could affect assemblies formation.Molecular dynamics simulations combined with electron microscopy confirmed distinct levels of macromolecular structures: from oligomers to fibrillar bundles, by applying single point mutations or N-terminal chemical modifications in the sequences.These results suggest that the self-assembly process could be finetuned by sequence modification, allowing widespread applications where specific levels of assembly stages need to be maintained.