Abstract Almost all commercial proteins are purified using ammonium sulfate precipitation. Protein-polymer conjugates are synthesized from pure starting materials, and the struggle to separate conjugates from polymer, native protein, and from isomers has vexed scientists for decades. We have discovered that covalent polymer attachment has a transformational effect on protein solubility in salt solutions. Here, protein-polymer conjugates with a variety of polymers, grafting densities, and polymer lengths are generated using atom transfer radical polymerization. Charged polymers increase conjugate solubility in ammonium sulfate and completely prevent precipitation even at 100% saturation. Atomistic molecular dynamic simulations show the impact is driven by an anti-polyelectrolyte effect from zwitterionic polymers. Uncharged polymers exhibit polymer length-dependent decreased solubility. The differences in salting-out are then used to simply purify mixtures of conjugates and native proteins into single species. Increasing protein solubility in salt solutions through polymer conjugation could lead to many new applications of protein-polymer conjugates.
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This content will become publicly available on May 6, 2027
Role of Polymer–Protein Interactions in the Dynamics of Polymer-Integrated Protein Crystals
- PAR ID:
- 10682379
- Publisher / Repository:
- ACS Publications
- Date Published:
- Journal Name:
- Journal of the American Chemical Society
- Volume:
- 148
- Issue:
- 17
- ISSN:
- 0002-7863
- Page Range / eLocation ID:
- 18080 to 18094
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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