Investigation on PEGylation Strategy of Recombinant Human interleukin-1 Receptor Antagonist

Bioorg Med Chem. 2007 Aug 15;15(16):5396-405. doi: 10.1016/j.bmc.2007.05.061. Epub 2007 May 31.


Although PEGylation is a potential approach to prolong the half-lives and reduce the dosing frequency of therapeutic proteins, conjugation behaviors of polymer have pivotal effects on the remaining bioactivities of the derivatives. In this study, the PEGylation strategy of recombinant human interleukin-1 receptor antagonist was investigated. The random conjugation of polyethylene glycol to amino groups on the protein resulted in a severe loss of activity and only retained 9.8% of the activity. In contrast, the PEGylation at the thiol groups had moderate effects on the bioactivity of protein and 40% of activity was conserved. The results suggested that the thiol-target PEGylation was more beneficial for IL-1ra.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, High Pressure Liquid
  • Crystallography, X-Ray
  • Esters / chemistry
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / antagonists & inhibitors*
  • Interleukin 1 Receptor Antagonist Protein / chemistry
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Maleimides / chemistry
  • Models, Molecular
  • Molecular Structure
  • Polyethylene Glycols / chemistry*
  • Protein Structure, Tertiary
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Esters
  • Interleukin 1 Receptor Antagonist Protein
  • Maleimides
  • Recombinant Proteins
  • maleimide
  • Polyethylene Glycols