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Synthesis of glycopolymers for the study of lectin-carbohydrate interactions

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Gou, Yanzi (2011) Synthesis of glycopolymers for the study of lectin-carbohydrate interactions. PhD thesis, University of Warwick.

Research output not available from this repository, contact author.
Official URL: http://webcat.warwick.ac.uk/record=b2561009~S1

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Abstract

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
Official Date: November 2011
Dates:
DateEvent
November 2011Submitted
Institution: University of Warwick
Theses Department: Department of Chemistry
Thesis Type: PhD
Publication Status: Unpublished
Supervisor(s)/Advisor: Haddleton, David M.
Sponsors: China Scholarship Council (CSC) ; University of Warwick
Extent: xxviii, 259 leaves : ill., charts
Language: eng

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