PEGylation of G-CSF using cleavable oligo-lactic acid linkage

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A new class of methoxy-poly(ethylene glycol) (mPEG) derivatives having a cleavable group of oligo-lactic acid (OLA) was synthesized by ring opening polymerization Of L-lactide using a terminal hydroxyl end of mPEG as an initiator. The synthesized mPEG derivatives had 0.8 and 3.6 lactic acid units based on the MALDI-TOF data. A terminal end group of mPEG-OLA was further activated with p-nitrophenyl chloroformate to produce mPEG-OLA-p-nitrophenyl carbonate (PC). mPEG-OLA-PC derivatives were conjugated to primary amine groups of recombinant human granulocyte-colony stimulating factor. PEGylated G-CSF conjugated with mPEG-OLA-PC derivatives consisted of native, mono-, di-, and tri-PEGylated species, and they did not show any apparent conformational changes even after PEGylation. When incubating in pH 7.4 buffer at 37 degreesC for 2 days, mPEG-OLA-G-CSF conjugates liberated mPEG by cleaving the OLA spacer, resulting in the gradual regeneration of G-CSF (C) 2003 Elsevier Science B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2003-04
Language
English
Article Type
Article
Keywords

COLONY-STIMULATING FACTOR; POLYETHYLENE-GLYCOL; SUPEROXIDE-DISMUTASE; POLY(ETHYLENE GLYCOL); MASS-SPECTROMETRY; IN-VIVO; PROTEINS; PURIFICATION; STABILITY; CHEMISTRY

Citation

JOURNAL OF CONTROLLED RELEASE, v.89, no.2, pp.271 - 284

ISSN
0168-3659
URI
http://hdl.handle.net/10203/12332
Appears in Collection
CH-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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