Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.576411
Title: Peptide nanomaterials : characterisation of enzyme-assisted self-assembly
Author: Hughes, Meghan
ISNI:       0000 0004 2744 4920
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2012
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Abstract:
Aromatic peptide amphiphiles have emerged as molecular building blocks which form a variety supramolecular peptide nanostructures by molecular self-assembly. These are short peptide chains, generally less than five amino acids in length, chemically modified at the N-terminus with an aromatic group to aid assembly. In aqueous environments, they form supramolecular structures by (Ss(B-stacking of aromatic moieties and hydrogen bonding between peptide chains, typically in a (Sb(B-sheet fashion, with additional stabilisation possible from the amino acid side chains. Enzymes have been employed to control the assembly process by converting non-assembling precursors into self-assembling molecules, thus initiating molecular self-assembly. Variation of the peptide sequence has allowed for access to a range of nanoscale architectures including tubes, fibres,1, 2 twisted ribbons, tapes, sheets, spheres and rings. The morphology is influenced by both the route of assembly and the amino acid sequence within the peptide chain. Therefore, by understanding the amino acid sequence/structure relationships, may allow rational design and tailoring of the materials for purpose. By utilising thermolysin triggered self-assembly of Fmoc-SF-OMe by condensation of the amino acid precursors, a system which operates under thermodynamic control, the production of the first micron sized two-dimensional peptide nanostructures from chiral molecular building blocks was demonstrated. The lateral self-assembly is enabled by the reversible nature of the system, favouring the thermodynamic product (extended sheets) over kinetically favoured 1 dimensional structures. Furthermore, the use of a fully reversible system allows for the thermodynamically favoured product to be formed reproducibly. In turn, by direct comparison of four self-assembling aromatic peptide amphiphiles, Fmoc-SF-OMe, Fmoc-SL-OMe, Fmoc-TF-OMe and Fmoc-TL-OMe, it is possible to monitor the influence of small changes in the molec ular structure within the peptidic tail on nanoscale architecture. As the hydrophobic effect if known to be a major driving force in molecular self-assembly, typically aromatic peptide amphiphiles have been designed to be hydrophobic in nature, and contain aromatic amino acid residues. In order to introduce a new chemical functionality to peptide nanostructures, terminating hydrophilic amino acid residues are introduced to the peptide chain. Subtilisin triggered self-assembly of Fmoc-YT-OH, Fmoc-YS-OH, Fmoc-YN-OH and Fmoc-YQ-OH is monitored in order to rationalise the influence of different amino acid residues within the peptide chain on nanoscale structure. Finally, as the enzymes employed to triggered self-assembly are present in biological systems, it was possible to convert non-assembling precursors into self-assembling aromatic peptide amphiphiles in vivo. E. Coli was cultured with an over expression of the enzyme alkaline phosphatase. By addition of the self-assembly precursors, it was then possible to monitor the anti-microbial effects of five different aromatic peptide amphiphiles; Fmoc-FY-OH, Fmoc-YT-OH, Fmoc-YS-OH, Fmoc-YN-OH and Fmoc-YQ-OH. A differential anti-microbial response was observed for E. Coli after treatment with the aromatic peptide amphiphiles.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.576411  DOI: Not available
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