title: Modification of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and its derivative ND 28 with polyethylene glycol.
abstract: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been obtained from genetically engineered Escherichia coli as an unglycosylated protein. Both native glycosylated hG-CSF and rhG-CSF are rapidly cleared from the circulation, which may limit their effectiveness for clinical use. To improve this biological property, rhG-CSF and its derivative ND 28, which has a higher specific activity than does rhG-CSF, were modified with polyethylene glycol (PEG). Modified rhG-CSF and ND 28 in which 1 to 3 mol of PEG were bound, were purified by two-step chromatography and characterized by several methods. The results of 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-CSF and ND 28 enhanced the stability of rhG-CSF and ND 28 and decreased the plasma clearance rate, which led to more effective hemopoiesis.
authors.affiliation: Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd.
authors.forename: M
authors.initials: M
authors.lastname: Yamasaki
authors.forename: M
authors.initials: M
authors.lastname: Asano
authors.forename: M
authors.initials: M
authors.lastname: Okabe
authors.forename: M
authors.initials: M
authors.lastname: Morimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Yokoo
mesh_terms: D004355:Drug Stability; D016179:Granulocyte Colony-Stimulating Factor / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000302:isolation & purification / Q000493:pharmacokinetics; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; C072115:nartograstim