Improvements in protein PEGylation: pegylated interferons for treatment of hepatitis C

J Control Release. 2001 May 14;72(1-3):217-24. doi: 10.1016/s0168-3659(01)00277-2.


Poly(ethyleneglycol) or PEG has proven to be of great value for a range of biomedical applications. A review the properties of PEG that lead to these applications is reported. Emphasis is placed on pharmaceutical uses of PEG--proteins, with specific discussion of the attributes of PEGylated alpha-interferon for treatment of hepatitis C. In this latter case the choice of PEG reagent is critical to the properties of the drug, and therefore a brief presentation of PEG reagents for protein PEGylation will be given. PEGylation chemistries can be divided into first- and second-generation approaches. The first-generation chemistries are generally restricted to low-molecular-weight methoxy-PEGs because of the problem of diol contamination and resulting difunctional reagents. Problems with weak linkages and side reactions are also encountered. Second-generation PEGylation reagents avoid weak linkages and side reactions. Also they can be purified to remove diol contaminants, and as a consequence, high-molecular-weight PEGs can be used. These relatively simple chemical advances have given new vigor to PEGylation as a technology. The benefits of using high-molecular-weight, second-generation PEG reagents are demonstrated by using PEG--alpha-interferon as an example. In this case it is observed that a greatly improved drug is provided for treatment of hepatitis C.

Publication types

  • Review

MeSH terms

  • Animals
  • Hepatitis C / drug therapy*
  • Humans
  • Interferons / administration & dosage*
  • Interferons / therapeutic use*
  • Polyethylene Glycols / chemistry*
  • Recombinant Proteins


  • Recombinant Proteins
  • Polyethylene Glycols
  • Interferons