Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.775316
Title: Hyaluronan (HA) glycopolymers and self-assembling HA-binding peptides : a synthetic toolbox for probing HA-peptide/protein interactions and creating supramolecular HA biomaterials
Author: Collis, D. W. P.
ISNI:       0000 0004 7962 4923
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2019
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Abstract:
Hyaluronan (HA) is a highly abundant anionic polysaccharide found throughout mammalian connective tissues. Unlike other glycosaminoglycans, HA is non-sulfated and its alternating chemical structure is invariable. Despite its simplicity, HA is involved in the extracellular matrix organization and many other aspects of cell behaviour. Using HA as a model polymer, we took inspiration to design and synthesize glycopolymers based on HA and self-assembling HA-binding peptides. Glycopolymers provide an alternative to conventional polysaccharides by offering the possibility to display sugars across the polymer at defined densities, while providing a robust polymer backbone rather than the glycosidic bonds, potentially forming more stable biomaterials with similar biological activity. The synthesis of alternating, homo and statistical HA neoglycopolymers was achieved via reversible addition fragmentation chain transfer (RAFT) polymerisation. The monosaccharides are grafted onto the polymers backbone by post-polymerisation click reactions to achieve the desired glycopolymers. These glycopolymers share some properties of native HA, such as water solubility and negative charge. Binding studies showed the ability of these glycopolymers to interact with HA-binding peptides and proteins, whilst not presenting any cytotoxicity behaviour. This approach provides control over the type and variation of saccharides, not be possible using natural HA, suggesting their potential use in mechanistic studies to understand HA binding processes. Peptides, on the other hand, have received increasing interest as potential biomaterials due to their inherent biocompatibility and biodegradability. Peptides can be engineered to drive their self-assembly into defined nanostructures, such as micelles and fibers. By designing HA-binding peptides with self-assembling properties, their combination with natural HA resulted in the formation of supramolecular hydrogels or membranes. Whilst the synthesis of large molecules like proteins is still a challenge, peptide synthesis is relatively simple and their self-assembly can result in nanomaterials with structures and functions resembling proteins. The synthetic molecules described in this thesis can be used as probes to better understand the role and binding of HA as well as reveal new applications.
Supervisor: Not available Sponsor: European Union (FP7)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.775316  DOI: Not available
Keywords: Engineering and Material Science ; glycopolymers ; biomaterials
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