Peer-Reviewed Journal Details
Mandatory Fields
Antonik, PM,Eissa, AM,Round, AR,Cameron, NR,Crowley, PB
2016
August
Biomacromolecules
Noncovalent PEGylation via Lectin-Glycopolymer Interactions
Published
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Optional Fields
SMALL-ANGLE SCATTERING RAY SOLUTION SCATTERING FUCOSE-BINDING LECTIN BIOLOGICAL MACROMOLECULES NMR-SPECTROSCOPY REVERSIBLE PEGYLATION PROTEIN CONJUGATION POLYMER CONJUGATE CLICK CHEMISTRY BEAMLINE
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2719
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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.
10.1021/acs.biomac.6b00766
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