Controlled self-assembly of small helical beta-peptides

Submission note: A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy to the Department of Chemistry and Physics, School of Molecular Sciences, College of Science, Health and Engineering, La Trobe University, Bundoora.

Thesis with publications.

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The thesis describes a systematic study of the controlled formation of hierarchical nanostructures based of N-acetylated helical β3 -peptides. The peptides were designed to self-assemble in a head-to-tail fashion, via a 3-point supramolecular motif. The association of these core helices via second order interactions yields superstructures that can be controlled with physical and chemical environmental factors. The effect of solvent environment and the cross-sectional geometry of the fibres was studied with microscopy methods on isomeric tripeptides; it was found that a balance between solvophobic forces and van der Waals attraction allows the tuning of the superstructure between rope-like fibre bundles and dendritic assemblies. Synchrotron far-IR spectroscopic measurements confirmed that all three peptides had the same core folding geometry. The analysis of the vibrational spectra using DFT calculations revealed a strong effect of hydrogen bonding on the amide vibrational modes. The effect of the side chain polarity of the folding and self-assembly of N-acetyl β3 -peptides was also studied using a series of tetra-peptides of increasingly polar sidechains; the results confirmed that this family of peptides forms stable helices and self-assemble in any solvent environment irrespective of the side chain chemistry. Hence a secondary self-assembly motif was introduced by enclosing αhistidine residues between two β3 -segments to form “introns”. These peptides retained the ability to form fibres through the primary self-assembly motif; metal coordination of the histidine side chains yielded gelling in solution phase and regular arrays in surface deposits. Two-dimensional sheets of these metal coordination crosslinked introns exhibited conductivity comparable to common conductive polymers. Considering that target applications for the β3 -peptide based hierarchical nanomaterials is in the biomedical field, the toxicity of the peptides was also studied on C. elegans using a novel oral delivery method, and it was confirmed that the ingestion of N-acetylated β3 -peptides has no appreciable toxic effect. Hence, a novel class of versatile self-assembling nano materials has been established in this work that is suitable for a range of applications in fields as diverse as medicine and molecular electronics.