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Noncovalent PEGylation via lectin–glycopolymer interactions
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Antonik, Paweł M., Eissa, Ahmed M., Round, Adam R., Cameron, Neil R. and Crowley, Peter B. (2016) Noncovalent PEGylation via lectin–glycopolymer interactions. Biomacromolecules, 17 (8). pp. 2719-2725. doi:10.1021/acs.biomac.6b00766 ISSN 1525-7797.
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WRAFP_engineering-191216-submitted_revised_manuscript.pdf - Accepted Version - Requires a PDF viewer. Download (1117Kb) |
Official URL: http://dx.doi.org/10.1021/acs.biomac.6b00766
Abstract
PEGylation, the covalent modification of proteins with polyethylene glycol, is an abundantly used technique to improve the pharmacokinetics of therapeutic proteins. The drawback with this methodology is that the covalently attached PEG can impede the biological activity (e.g., reduced receptor-binding capacity). Protein therapeutics with “disposable” PEG modifiers have potential advantages over the current technology. Here, we show that a protein–polymer “Medusa complex” is formed by the combination of a hexavalent lectin with a glycopolymer. Using NMR spectroscopy, small-angle X-ray scattering (SAXS), size exclusion chromatography, and native gel electrophoresis it was demonstrated that the fucose-binding lectin RSL and a fucose-capped polyethylene glycol (Fuc-PEG) form a multimeric assembly. All of the experimental methods provided evidence of noncovalent PEGylation with a concomitant increase in molecular mass and hydrodynamic radius. The affinity of the protein–polymer complex was determined by ITC and competition experiments to be in the micromolar range, suggesting that such systems have potential biomedical applications.
Item Type: | Journal Article | ||||||||||
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Subjects: | R Medicine > RS Pharmacy and materia medica T Technology > TP Chemical technology |
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Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering | ||||||||||
Library of Congress Subject Headings (LCSH): | Protein engineering, Polyethylene glycol, Polymers -- Synthesis, Polymeric drug delivery systems, Pharmacokinetics | ||||||||||
Journal or Publication Title: | Biomacromolecules | ||||||||||
Publisher: | American Chemical Society | ||||||||||
ISSN: | 1525-7797 | ||||||||||
Official Date: | 8 August 2016 | ||||||||||
Dates: |
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Volume: | 17 | ||||||||||
Number: | 8 | ||||||||||
Page Range: | pp. 2719-2725 | ||||||||||
DOI: | 10.1021/acs.biomac.6b00766 | ||||||||||
Status: | Peer Reviewed | ||||||||||
Publication Status: | Published | ||||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||||
Date of first compliant deposit: | 21 December 2016 | ||||||||||
Date of first compliant Open Access: | 12 July 2017 | ||||||||||
Funder: | Teagasc (Organization), National university of Ireland, Galway, Leverhulme Trust (LT), European Cooperation in the Field of Scientific and Technical Research (Organization) (COST), Science Foundation Ireland (SFI) | ||||||||||
Grant number: | F/00128/BO (LT), TD10 03 Bioinspired Nanotechnologies (COST), 10/RFP/BIC2807, 13/CDA/2168 (SFI) |
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