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Glycopolymers with secondary binding motifs mimic glycan branching and display bacterial lectin selectivity in addition to affinity
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Jones, Mathew W., Otten, Lucienne, Richards, Sarah-Jane, Lowery, Richard, Phillips, Daniel J., Haddleton, David M. and Gibson, Matthew I. (2014) Glycopolymers with secondary binding motifs mimic glycan branching and display bacterial lectin selectivity in addition to affinity. Chemical Science, 5 (4). pp. 1611-1616. doi:10.1039/c3sc52982g ISSN 2041-6520.
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Official URL: http://dx.doi.org/10.1039/C3SC52982G
Abstract
The application of synthetic glycopolymers to anti-adhesive therapies has so far been limited by their lack of lectin specificity. Here we employ a macromolecular engineering approach to mimic glycan architecture. A new, 3-step tandem post-polymerisation methodology was developed which afforded precise control over both chain length and carbohydrate (galactose)-polymer backbone linker distance. This route also allowed a secondary binding (branched) motif to be introduced onto the linker, increasing specificity and affinity towards bacterial toxins without the need for extensive carbohydrate or organic chemistry. Sequential variation of this motif was found to dramatically alter both the affinity and the specificity of the glycopolymers towards two lectins, CTx and PNA, by up to 20-fold either via direct binding, or increased steric constraints. Using this method, a glycopolymer that showed increased specificity towards CTx was identified.
Item Type: | Journal Article | ||||||||||
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Subjects: | Q Science > QD Chemistry | ||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||||||||
Library of Congress Subject Headings (LCSH): | Polymers , Chemistry, Organic, Carbohydrates, Lectins | ||||||||||
Journal or Publication Title: | Chemical Science | ||||||||||
Publisher: | Royal Society of Chemistry | ||||||||||
ISSN: | 2041-6520 | ||||||||||
Official Date: | 1 April 2014 | ||||||||||
Dates: |
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Volume: | 5 | ||||||||||
Number: | 4 | ||||||||||
Page Range: | pp. 1611-1616 | ||||||||||
DOI: | 10.1039/c3sc52982g | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||||
Funder: | Birmingham Science City, European Regional Development Fund (ERDF), Higher Education Funding Council for England (HEFCE), Engineering and Physical Sciences Research Council (EPSRC), University of Warwick Postgraduate Research Scholarship |
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