Noncovalent PEGylation via Lectin–Glycopolymer Interactions

Antonik, Pawel; Eissa, Ahmed; Round, Adam; Cameron, Neil; Crowley, Peter

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.

Citation

Antonik, P., Eissa, A., Round, A., Cameron, N., & Crowley, P. (2016). Noncovalent PEGylation via Lectin–Glycopolymer Interactions. Biomacromolecules, 17(8), 2719-2725. https://doi.org/10.1021/acs.biomac.6b00766

• Journal Article Type: Article
• Online Publication Date: Jul 12, 2016
• Publication Date: Aug 8, 2016
• Deposit Date: Oct 5, 2016
• Publicly Available Date: Jul 12, 2017
• Journal: Biomacromolecules
• Print ISSN: 1525-7797
• Electronic ISSN: 1526-4602
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 8
• Pages: 2719-2725
• DOI: https://doi.org/10.1021/acs.biomac.6b00766
• Public URL: https://durham-repository.worktribe.com/output/1403419