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Title: A study into the self-assembly of bioactive peptide amphiphiles
Author: Kirkham, Steven
ISNI:       0000 0004 6494 1977
Awarding Body: University of Reading
Current Institution: University of Reading
Date of Award: 2017
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There are a vast array of different molecules which have shown the ability to self-assemble in solvent to form a range of nanostructures. Micelles are formed by surfactant-like molecules with hydrophobic and hydrophilic parts, and β-sheet fibrils are formed by peptide-based molecules. This self-assembly is driven through non-covalent interactions of the domains to form supramolecular assemblies. Peptide amphiphiles are one of these groups of selfassembling compounds. They can be purely peptidic (composed of hydrophobic and hydrophilic residues), or a combination of amino acids with hydrophobic lipid chains, hydrophilic polymers etc. The first part of the thesis concerns three different lipopeptides comprised of the same peptide sequence attached to differing numbers of palmitoyl lipid chains. The compounds are found to form micellar or bilayer structures, with different morphology and secondary structure characteristics, which may explain their differing bioactivities. The second part leads on from this and investigated the comparison between the self-assembly of another lipopeptide and its constituent peptide. The peptide formed twisted tapes, compared with fascinating raft-like structures with the lipopeptide, which to our knowledge had not previously been seen before with this class of biomolecule. In chapter 4, a dipeptide attached to a bulky aromatic fluorophore is explored through its self-assembly, and cytotoxicity and cellular uptake. Large twisted nanotapes were observed above an experimentally determined aggregation concentration, and the compound was found to be non-toxic and taken up into perinuclear regions of cells. Chapter 5 describes the self-assembly properties of an antifungal compound, amphotericin B, at concentrations above an experimentally determined aggregation point. It was found that it had a time-dependent change in secondary structure and formation of a mixture of cylindrical micelles and very long twisting tapes. In chapter 6, the self-assembly of another drug, daptomycin, is examined with and without calcium ions. Calcium is believed to be necessary for assembly to occur. No differences were observed here however, with similar aggregation concentrations and structures formed in both conditions. The final chapter consists of a report on the self-assembly properties of three polymer-peptide conjugates with hydrophilic central blocks and hydrophobic tyrosine end-caps, as well as preliminary experiments into their cytocompatibility when incorporated into alginate-based hydrogels. They were shown to form fibrils with different morphologies and β-sheet content, and our study shows the effect on self-assembly of midblock length and polymer type.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available