MODIFICATION OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF) AND ITS DERIVATIVE ND-28 WITH POLYETHYLENE-GLYCOL

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been obtained from genetically engineered Escherichia coli as an ungly cosylated protein. Both native glycosylated hG-CSF and rhG-CSF are rap idly cleared from the circulation, which may limit their effectiveness for clinical use. To improve this biological property, rhG-CSF and it s derivative ND 28, which has a higher specific activity than does rhG -CSF, were modified with polyethylene glycol (PEG). Modified rhG-CSF a nd ND 28 in which 1 to 3 mol of PEG were bound, were purified by two-s tep chromatography and characterized by several methods. The results o f their physicochemical characterization suggest that PEG-modification does not appreciably change the conformation of rhG-CSF and ND 28. As a result of the whole characterization, the PEG-modification of rhG-C SF and ND 28 enhanced the stability of rhG-CSF and ND 28 and decreased the plasma clearance rate, which led to more effective hemopoiesis.