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Abstract Polymer–protein hybrids are intriguing materials that can bolster protein stability in non‐native environments, thereby enhancing their utility in diverse medicinal, commercial, and industrial applications. One stabilization strategy involves designing synthetic random copolymers with compositions attuned to the protein surface, but rational design is complicated by the vast chemical and composition space. Here, a strategy is reported to design protein‐stabilizing copolymers based on active machine learning, facilitated by automated material synthesis and characterization platforms. The versatility and robustness of the approach is demonstrated by the successful identification of copolymers that preserve, or even enhance, the activity of three chemically distinct enzymes following exposure to thermal denaturing conditions. Although systematic screening results in mixed success, active learning appropriately identifies unique and effective copolymer chemistries for the stabilization of each enzyme. Overall, this work broadens the capabilities to design fit‐for‐purpose synthetic copolymers that promote or otherwise manipulate protein activity, with extensions toward the design of robust polymer–protein hybrid materials.
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Polymer conjugation of proteins as a synthetic post-translational modification to impact their stability and activity
For more than 40 years, protein–polymer conjugates have been widely used for many applications, industrially and biomedically. These bioconjugates have been shown to modulate the activity and stability of various proteins while introducing reusability and new activities that can be used for drug delivery, and to improve pharmacokinetic ability and stimuli-responsiveness. Techniques such as RDRP, ROMP and “click” have routinely been utilized for the development of well-defined bioconjugate and polymeric materials. The synthesis of bioconjugate materials often takes advantage of the natural amino acids present within the protein and peptide structures for a host of coupling chemistries. Polymer modification may elicit increased or decreased activity, activity retention under harsh conditions, and prolonged activity in vivo and in vitro , and introduce stimuli responsiveness. Bioconjugation has resulted in modulated thermal stability, chemical stability, storage stability, half-life and reusability. In this review we aim to provide a brief account of the field, highlight a wide range of behaviors caused by polymer conjugation, and provide directions for future work.
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- Award ID(s):
- 1749730
- PAR ID:
- 10088289
- Date Published:
- Journal Name:
- Polymer Chemistry
- Volume:
- 10
- Issue:
- 4
- ISSN:
- 1759-9954
- Page Range / eLocation ID:
- 434 to 454
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C8PY01399C
