Saccharides act important roles in many biological processes as recognition molecules, signalling molecules and adhesion molecules. However, due to the complexity and diversity of oligosaccharides the direct synthetic approaches cannot fully meet the demands for all of the pure and well-defined oligosaccharides being studied in glycobiology. The efficient synthesis of glycomimetics, glycopolymers, offers an attractive route to solve this problem. Thus, the synthesis and application of glycopolymers of various architectures has been extensively investigated. Meanwhile, In order to explore the mechanism of the lectin-carbohydrate interactions and to get a better understanding of the structure-function relationship of oligosaccharides, the assays employed in studies of lectin-carbohydrate interactions become much more sophisticated and accurate with fast development of various analytical approaches. In this work, well-defined glycopolymers were prepared by the combination of CCTP and CuAAC click reactions. Alkyne-containing polymer scaffolds were synthesised by CCTP, followed by post-modification of the clickable polymer scaffolds with sugar azides. Moreover, a library of well-defined synthetic glycopolymers featuring the same macromolecular properties (architecture, polydispersity, valency, polarity, etc.) with difference only in the densities of different sugars (mannose, galactose and glucose) were employed to investigate the influence of different pendant epitopes on the interactions with a model lectin Con A by the traditional methods. Additionally, two powerful modem detection techniques QCM-D and SPR were also exploited to investigate the interactions of the lectin Con A, PNA, or DC-SIGN with a series of different glycopolymers. The diversities of binding properties contributed by different clustering parameters can make it possible to define the structures of the multivalent ligands and densities of binding epitopes for specific functions in the lectin-carbohydrate interactions. These conclusions can be employed as the springboard to develop new glycopolymeric drugs and therapeutic agents and to assess the mechanisms by which they work.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:549883 |
| Date | January 2011 |
| Creators | Gou, Yanzi |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://wrap.warwick.ac.uk/79688/ |
Page generated in 0.0013 seconds