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Structure-Activity Effects in Self-Assembled Multivalent (SAMul) Polyanion Binding.

Albanyan , Buthaina (2016) Structure-Activity Effects in Self-Assembled Multivalent (SAMul) Polyanion Binding. PhD thesis, University of York.

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Abstract

We have synthesized several self-assembled multivalent (SAMul) systems based on two parts; a hydrophobic part as the driving force for self-assembly, and a cationic hydrophilic part as the binding site for polyanions. A number of modified ligand displays were synthesized in order to investigate structure-activity relationship and their effects on self-assembly of such systems as well as their selectivities towards binding different polyanions (heparin and DNA). The first three systems were synthesized using unsaturated fatty acids (containing alkene groups), this resulted in different self-assembly abilities, in addition to different selectivities towards the biological polyanions (heparin and DNA). In an attempt to stabilize those systems, we cross-linked the alkene groups – however the binding did not improve. We modified the ligand binding sites, using different amines. This also resulted in different self-assembly preferences in addition to selectivities for binding heparin and DNA. Alternative approaches to stabilizing displays of heparin-binding ligands were tested using a branched scaffold with a high density of positive charges on the surface groups, gold nanoparticles and a ligand-polymer conjugate approach. Finally, a multicomponent approach was employed in this work. PEG-lipid additives, were introduced to our SAMul systems to test their impact on binding heparin and DNA. Adding PEG-lipids to our SAMul demonstrated that a simple uncharged species can have an influence on binding strength in the clinically relevant serum medium. In addition, the multicomponent approach was also performed on two compounds using a multi component MalB assay. This showed that this approach may in the future help rapidly identify mixtures of self-assembling components which have positive synergistic effects. In each study we have learned more about the structural impact of ligand designed display in polyanion binding – information which should prove useful in the future design of systems with clinical relevance.

Item Type: Thesis (PhD)
Related URLs:
Academic Units: The University of York > Chemistry (York)
Depositing User: Mrs Buthaina Albanyan
Date Deposited: 31 Jan 2017 15:15
Last Modified: 31 Jan 2017 15:15
URI: http://etheses.whiterose.ac.uk/id/eprint/16055

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