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Soluble Zwitterionic Poly(sulfobetaine) Destabilizes Proteins

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    Soluble Zwitterionic Poly(sulfobetaine) Destabilizes Proteins
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    • Lydia Kisley
      Lydia Kisley
      Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
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    • Kali A. Miller
      Kali A. Miller
      Beckman Institute for Advanced Science and Technology  and  Department of Chemistry, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
      More by Kali A. Miller
      Orcidhttp://orcid.org/0000-0003-3632-0615
    • Caitlin M. Davis
      Caitlin M. Davis
      Department of Chemistry  and  Department of Physics, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
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    • Drishti Guin
      Drishti Guin
      Department of Chemistry, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
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    • Elizabeth A. Murphy
      Elizabeth A. Murphy
      Beckman Institute for Advanced Science and Technology  and  Department of Chemistry, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
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    • Martin Gruebele*
      Martin Gruebele
      Beckman Institute for Advanced Science and Technology,  Department of Chemistry  and  Department of Physics, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
      *E-mail: [email protected]. Phone: (217)-333-6136.
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      Orcidhttp://orcid.org/0000-0001-9291-8123
    • Deborah E. Leckband*
      Deborah E. Leckband
      Beckman Institute for Advanced Science and Technology  and  Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801, United States
      *E-mail: [email protected]. Phone: (217)-244-0793.
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      Orcidhttp://orcid.org/0000-0002-7557-766X
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    Biomacromolecules

    Cite this: Biomacromolecules 2018, 19, 9, 3894–3901
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    https://doi.org/10.1021/acs.biomac.8b01120
    Published July 31, 2018
    Copyright © 2018 American Chemical Society
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    Abstract

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    The widespread interest in neutral, water-soluble polymers such as poly(ethylene glycol) (PEG) and poly(zwitterions) such as poly(sulfobetaine) (pSB) for biomedical applications is due to their widely assumed low protein binding. Here we demonstrate that pSB chains in solution can interact with proteins directly. Moreover, pSB can reduce the thermal stability and increase the protein folding cooperativity relative to proteins in buffer or in PEG solutions. Polymer-dependent changes in the tryptophan fluorescence spectra of three structurally-distinct proteins reveal that soluble, 100 kDa pSB interacts directly with all three proteins and changes both the local polarity near tryptophan residues and the protein conformation. Thermal denaturation studies show that the protein melting temperatures decrease by as much as ∼1.9 °C per weight percent of polymer and that protein folding cooperativity increases by as much as ∼130 J mol–1 K–1 per weight percent of polymer. The exact extent of the changes is protein-dependent, as some proteins exhibit increased stability, whereas others experience decreased stability at high soluble pSB concentrations. These results suggest that pSB is not universally protein-repellent and that its efficacy in biotechnological applications will depend on the specific proteins used.

    Copyright © 2018 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.biomac.8b01120.

    • Characterization of proteins and polymer, data of λ12 and WW domain folding with PEG and variable ionic strength, tables and figures with detailed fitting parameters (PDF).

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    This article is cited by 25 publications.

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    Biomacromolecules

    Cite this: Biomacromolecules 2018, 19, 9, 3894–3901
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.biomac.8b01120
    Published July 31, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

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