Therapeutic Protein–Polymer Conjugates: Advancing Beyond PEGylation
Abstract
Protein-polymer conjugates are widely used as therapeutics. All Food and Drug Administration (FDA)-approved protein conjugates are covalently linked to poly(ethylene glycol) (PEG). These PEGylated drugs have longer half-lives in the bloodstream, leading to less frequent dosing, which is a significant advantage for patients. However, there are some potential drawbacks to PEG that are driving the development of alternatives. Polymers that display enhanced pharmacokinetic properties along with additional advantages such as improved stability or degradability will be important to advance the field of protein therapeutics. This perspective presents a summary of protein-PEG conjugates for therapeutic use and alternative technologies in various stages of development as well as suggestions for future directions. Established methods of producing protein-PEG conjugates and new approaches utilizing controlled radical polymerization are also covered.
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Protein-polymer conjugates with polyethylene glycol (PEG) have improved their half-life, increased physical stability, and rendered them immune-free.
“Protein-polymer conjugates polyethylene glycol (PEG) have improved their half-life, increased the physical stability, and rendered them immune-free.24”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [24]
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- Authors
- Pelegri-O’Day, E. M., Lin, E.-W., & Maynard, H. D.
- Affiliations
- California NanoSystems Institute (US)
- Corresponding author
- Maynard, Heather D.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-09-30
- Volume
- 136
- Issue
- 41
- Pages
- 14323-14332
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2315302880
- Cited by
- 622
- References
- 116
- Citations by year
- 2026: 23 · 2025: 30 · 2024: 42 · 2023: 50 · 2022: 51 · 2021: 50 · 2020: 69 · 2019: 59 · 2018: 75 · 2017: 58 · 2016: 64 · 2015: 46 · 2014: 4
- FWCI
- 25.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Division of Chemistry (CHE-1112550)
- Department of Chemistry and Biochemistry, University of California, Los Angeles
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- protein-polymer conjugates, PEGylation, polyethylene glycol, therapeutic proteins, pharmacokinetics, half-life extension, controlled radical polymerization, drug stability, conjugation methods
- MeSH terms
- Models, Molecular, Polyethylene Glycols, Proteins, Molecular Structure, Polymerization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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