Site-specific pegylation of therapeutic proteins

Jonathan K. Dozier, Mark D Distefano

Research output: Contribution to journalReview article

80 Citations (Scopus)

Abstract

The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as well as increasing the cost of therapy. One of the main strategies to alleviate these problems is to link a polyethylene glycol (PEG) group to the protein of interest. This process, called PEGylation, has grown dramatically in recent years resulting in several approved drugs. Installing a single PEG chain at a defined site in a protein is challenging. Recently, there is has been considerable research into various methods for the site-specific PEGylation of proteins. This review seeks to summarize that work and provide background and context for how site-specific PEGylation is performed. After introducing the topic of site-specific PEGylation, recent developments using chemical methods are described. That is followed by a more extensive discussion of bioorthogonal reactions and enzymatic labeling.

Original languageEnglish (US)
Pages (from-to)25831-25864
Number of pages34
JournalInternational journal of molecular sciences
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2015

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proteins
Proteins
Polyethylene glycols
glycols
polyethylenes
drugs
Therapeutics
excretion
Modern 1601-history
medicine
Pharmaceutical Preparations
Labeling
marking
Medicine
installing
therapy
History
histories
degradation
costs

Keywords

  • Chemical modification
  • Enzymatic modification
  • PEGylation
  • Protein PEGylation
  • Site specific modification
  • Therapeutic proteins

Cite this

Site-specific pegylation of therapeutic proteins. / Dozier, Jonathan K.; Distefano, Mark D.

In: International journal of molecular sciences, Vol. 16, No. 10, 01.10.2015, p. 25831-25864.

Research output: Contribution to journalReview article

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