title: Effects of site-specific polyethylene glycol modification of recombinant human granulocyte colony-stimulating factor on its biologic activities.
abstract: BACKGROUND
  Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a long-chain cytokine that is administered to stimulate the production of white blood cells (WBCs) to reduce the risk of serious infection in immunocompromized patients. However, to achieve sustained stimulation of WBC production, rhG-CSF must be administered frequently, thus limiting its clinical use.
  
  
  METHODS
  We conjugated rhG-CSF with linear monomethoxy-polyethylene glycol (PEG) maleimide at amino acid residue Cys(17) to test our hypothesis that this could extend the in vivo half-life of rhG-CSF in blood.
  
  
  RESULTS
  The mono-PEG rhG-CSF became more stable to pH, temperature, and enzyme degradation in vitro, and had granulopoietic activity that was superior to the unmodified form in vivo. The granulopoietic activity of PEG-G-CSF was 2.82-fold greater than that of unmodified G-CSF.
  
  
  CONCLUSIONS
  These results indicate that the thiol-specific PEGylation remarkably prolonged the half-life of rhG-CSF and represents a novel strategy to address the more clinically acceptable therapeutic application of hemopoietic growth factor.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hao
authors.forename: Junhui
authors.initials: J
authors.lastname: Chen
authors.forename: Xinchang
authors.initials: X
authors.lastname: Wang
authors.forename: Haowen
authors.initials: H
authors.lastname: Zhu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Rong
mesh_terms: D000818:Animals; D002460:Cell Line; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D011994:Recombinant Proteins; D013696:Temperature; D014357:Trypsin / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D014357:Trypsin