The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity
Open accessAbstract
Treatment with therapeutic proteins is an attractive approach to targeting a number of challenging diseases. Unfortunately, the native proteins themselves are often unstable in physiological conditions, reducing bioavailability and therefore increasing the dose that is required. Conjugation with poly(ethylene glycol) (PEG) is often used to increase stability, but this has a detrimental effect on bioactivity. Here, we introduce conjugation with zwitterionic polymers such as poly(carboxybetaine). We show that poly(carboxybetaine) conjugation improves stability in a manner similar to PEGylation, but that the new conjugates retain or even improve the binding affinity as a result of enhanced protein–substrate hydrophobic interactions. This chemistry opens a new avenue for the development of protein therapeutics by avoiding the need to compromise between stability and affinity.
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Cites
Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives
Knop, K., Hoogenboom, R., Fischer, D., & Schubert, U. S. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.200902672 · Cited by 3,533
PEGylation of therapeutic proteins
Jevševar, S., Kunstelj, M., & Porekar, V. G. (2010) · Biotechnology Journal · doi:10.1002/biot.200900218 · Cited by 681
Cited by
Polymer–drug conjugate therapeutics: advances, insights and prospects
Ekladious, I., Colson, Y. L., & Grinstaff, M. W. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0005-0 · Cited by 855
In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles
Arami, H., Khandhar, A., Liggitt, D., & Krishnan, K. M. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00541h · Cited by 830
Cancer nanomedicine: from targeted delivery to combination therapy
Xu, X., Ho, W., Zhang, X., Bertrand, N., & Farokhzad, O. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.01.001 · Cited by 693
Anti-PEG antibodies in the clinic: Current issues and beyond PEGylation
Zhang, P., Sun, F., Liu, S., & Jiang, S. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.06.040 · Cited by 688
Self-citationTherapeutic Protein–Polymer Conjugates: Advancing Beyond PEGylation
Pelegri-O’Day, E. M., Lin, E.-W., & Maynard, H. D. (2014) · Journal of the American Chemical Society · doi:10.1021/ja504390x · Cited by 622
Metadata
- Authors
- Keefe, A. J., & Jiang, S.
- Venue
- Nature Chemistry
- Published
- 2011-12-11
- Volume
- 4
- Issue
- 1
- Pages
- 59-63
- ISSN
- 1755-4330 (ISSN-L)
- 1755-4349
- OpenAlex
- W2009278211
- Cited by
- 576
- References
- 2
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- green
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- Keefe, A. J., & Jiang, S. (2012). Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity. Nature Chemistry. https://doi.org/10.1038/nchem.1213
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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