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Title: Post-modification strategies for polymeric cyclic peptide nanotubes
Author: Barlow, Tammie R.
ISNI:       0000 0004 6496 6875
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2017
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Self-assembly is a powerful process by which complex architectures can be achieved from single monomer units for a diverse range in applications from drug delivery to nano-electronics, an excellent example of which is self-assembled cyclic peptide nanotubes. The addition of polymers greatly enhances the potential applications of cyclic peptide nanotubes, however, there lacks a fundamental understanding on how this affects assembly, and whether it can be controlled by environmental manipulation. Additionally, there are few synthetic methods by which it is possible to access more complex polymeric architectures without the need for complex conjugation strategies. As such the present work aims to further develop a scope of synthetic possibilities for polymeric cyclic peptide nanotubes, generating materials by which it is possible to probe the self-assembly properties of these complex supramolecular systems. Initially the polymerisation of poly(bromo ethyl acrylate) (BEA) is explored via reversible addition-fragmentation chain transfer polymerisation (RAFT) and the post-modification possibilities this reactive polymeric precursor provides. From this, a library of polymer materials from a pBEA precursor via nucleophilic substitution with a range of nucleophiles can be generated. From this, the reactive pBEA polymers are combined with self-assembling cyclic peptides, without any unwanted side reactions. The self-assembly of these CP-pBEA conjugates was characterised in solution by SANS and SLS. From the CP-pBEA conjugates, it is possible to generate a range of materials, and the self-assembly of various nanotubular systems can be studied. These materials include a glycopolymer conjugate that forms sugar coated nanotubes in water, as determined by SANS, and displays interesting lectin binding properties. Furthermore, synthesis of highly charged polyelectrolyte-peptide conjugates was be carried out. The self-assembly of these polyelectrolyte conjugates could be readily manipulated by controlling the ionic strength of the solution. Finally, the cell-penetration of charged copolymers of poly(poly(ethylene glycol) methyl ether acrylate) (pPEGA) conjugates were studied to determine whether charge or self-assembly has a greater effect on cellular uptake. It was identified that self-assembly results in far greater in vitro cell penetration than for charged analogues. This thesis in its entirety reflects a thorough design strategy for the synthesis of complex materials; from the development of novel synthetic strategies and post-polymerisation modifications, through to supramolecular characterisation and a finally demonstration of the materials as an application for drug delivery in vitro.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QD Chemistry