Therapeutic Protein–Polymer Conjugates: Advancing Beyond PEGylation

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 significa...

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Published inJournal of the American Chemical Society Vol. 136; no. 41; pp. 14323 - 14332
Main Authors Pelegri-O’Day, Emma M, Lin, En-Wei, Maynard, Heather D
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 15.10.2014
Subjects
blood flow
chemical bonding
developmental stages
drugs
Food and Drug Administration
half life
Models, Molecular
Molecular Structure
patients
pharmacokinetics
polyethylene glycol
Polyethylene Glycols - chemistry
Polyethylene Glycols - therapeutic use
Polymerization
Proteins - chemistry
Proteins - metabolism
therapeutics
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Summary: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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ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/ja504390x