PEGylation of G-CSF using cleavable oligo-lactic acid linkage.
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 degrees C for 2 days, mPEG-OLA-G-CSF conjugates liberated mPEG by cleaving the OLA spacer, resulting in the gradual regeneration of G-CSF.
Choi
Seung Ho
SH
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, South Korea.
Lee
Haeshin
H
Park
Tae Gwan
TG
D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics*; D013678:Technology, Pharmaceutical / Q000379:methods*
D019344:Lactic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol