Effects of Site-Specific Polyethylene Glycol Modification of Recombinant Human Granulocyte Colony-Stimulating Factor on its Biologic Activities
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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.
We conjugated rhG-CSF with linear monomethoxy-polyethylene glycol (PEG) maleimide at amino acid residue Cys17 to test our hypothesis that this could extend the in vivo half-life of rhG-CSF in blood.
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.
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.
- Effects of Site-Specific Polyethylene Glycol Modification of Recombinant Human Granulocyte Colony-Stimulating Factor on its Biologic Activities
Volume 20, Issue 6 , pp 357-362
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- 1. State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, Nanjing University, 22 HanKou Road, Nanjing, 210093, People’s Republic of China
- 2. Biopharmaceutical Institute of Jiangsu Wuzhong, Suzhou, Jiangsu, People’s Republic of China