Synthesis of glycopolymers for the study of lectin-carbohydrate interactions
Gou, Yanzi (2011) Synthesis of glycopolymers for the study of lectin-carbohydrate interactions. PhD thesis, University of Warwick.Full text not available from this repository.
Official URL: http://webcat.warwick.ac.uk/record=b2561009~S1
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 modern 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.
|Item Type:||Thesis or Dissertation (PhD)|
|Subjects:||Q Science > QD Chemistry|
|Library of Congress Subject Headings (LCSH):||Glycomics, Lectins, Carbohydrates, Oligosaccharides|
|Institution:||University of Warwick|
|Theses Department:||Department of Chemistry|
|Supervisor(s)/Advisor:||Haddleton, David M.|
|Sponsors:||China Scholarship Council (CSC) ; University of Warwick|
|Extent:||xxviii, 259 leaves : ill., charts|
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