Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.692457
Title: Binding biological polyanions : understanding and controlling binding mode in order to achieve controlled nanoscale assembly
Author: Chan, Ching Wan
Awarding Body: University of York
Current Institution: University of York
Date of Award: 2016
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Abstract:
This thesis explores polyanion binding and sensing using varirty of different approaches and aims to understand and manipulate these interactions. Amine-functionalised pyrene derivatives Py-G1 and Py-DAPMA can act as effective heparin sensors in competitive media using a ratiometric fluorescence sensing approach. The assembly of Py-G1 into pre-formed self-assembled multivalent (SAMul) nanostructures provides it with a significant (order of magnitude) advantage in terms of the dynamic range of sensory response over the non-SAMul Py-DAPMA in buffer. In the presence of serum, both ligands can still detect heparin ratiometrically, however, the SAMul sensing mechanism of Py-G1 is switched off. Three series of SAMul dendrons based on L or D lysine and focal point hydrophobic groups, either pyrene or hydrocarbon chains, have been developed. Their ability to exhibit different chiral binding preferences towards chiral polyanions DNA and heparin have been studied. The way in which the ligands are displayed, which in turn depends on the nature of the hydrophobic component and the overall structural characteristics, are absolutely critical. Insertion of a simple linker allows expression of the chiral information at the nanoscale surface. The interaction between heparin and Mallard Blue (Mal-B) or a series of SAMul heparin binders are explored by NMR spectroscopy. The choice of buffer has significant impact on Mal-B/heparin binding, but precipitation of the Mal-B:heparin complex limits the opportunity for NMR analysis. NMR provides some insight to the binding events at the nanoscale and appears particularly useful for uncovering the role of ligands and dynamics in mediating binding with the best binder appearing to have best resolved ligand NMR resonances. The ability of C22-G1 and Py-G1 to ast as “nanoglue”, causing adhesion between polyanions and carbon nanotubes was studied. Both can self-assemble and bind to DNA and SWCNT respectively and C22-G1 is a better DNA and SWCNT binder. Although the attempt to quantitatively assay simultaneous DNA and SWCNT binding was unsuccessful, TEM imaging clearly allowed onto monitor the binding of DNA and CNT, and demonstrated that our synthetic nanoglue system causes them to co-assemble.
Supervisor: Smith, David K. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.692457  DOI: Not available
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