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Molecular Sieving on the Surface of a Protein Provides Protection Without Loss of Activity

Authors

  • Mi Liu,

    1. Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Wolfgang-Pauli Str. 10, 8093 Zürich, Switzerland
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  • Pasquale Tirino,

    1. Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Wolfgang-Pauli Str. 10, 8093 Zürich, Switzerland
    2. Department of Chemistry “Paolo Corradini”, University Federico II, Via Cinthia, I-80126 Naples, Italy
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  • Milos Radivojevic,

    1. Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Wolfgang-Pauli Str. 10, 8093 Zürich, Switzerland
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  • Daniel J. Phillips,

    1. Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, UK
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  • Matthew I. Gibson,

    1. Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, UK
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  • Jean-Christophe Leroux,

    1. Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Wolfgang-Pauli Str. 10, 8093 Zürich, Switzerland
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  • Marc A. Gauthier

    Corresponding author
    1. Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Wolfgang-Pauli Str. 10, 8093 Zürich, Switzerland
    • Swiss Federal Institute of Technology Zürich (ETH Zürich), Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Wolfgang-Pauli Str. 10, 8093 Zürich, Switzerland.
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Abstract

Tethering polymers to surfaces represents the cornerstone of a wide range of applications, including the stabilization of colloids/biomolecules and the preparation of functional coatings. Unfortunately, despite the prevalence of protein-tethered polymers in the pharmaceutical sector, the analysis of such polymer monolayers on a molecular level is difficult. In this work, simple 1H NMR spectroscopy and the catalytic properties of α-chymotrypsin are used to analyze the conformational/permeability properties of protein-bound monolayers of poly(oligoethyleneglycol monomethylether methacrylate) (pOEGMA), a biocompatible comb-polymer of interest in the biomedical field. By analyzing >100 distinct conjugates of α-chymotrypsin and pOEGMA, a detailed picture of the behavior of pOEGMA on the surface of a protein was obtained. Remarkably, control of polymer conformation and inter-penetration produced a thus far overlooked molecular sieving effect. The application of this effect for the “smart” PEGylation of proteins is portrayed, from which insight is provided for the design of other therapeutic bioconjugates and functional coatings with selective permeability properties.

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