Poly(ethylene glycol) conjugation of G-CSF using cleavable oligo-lactic acid spacer = 생분해성 올리고 락트산이 도입된 폴리에틸렌 글리콜의 G-CSF 접합에 관한 연구

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A new class of mPEG derivatives having cleavable oligo lactic acid was synthesized by ring opening polymerization of L-lactide using a terminal hydroxyl end of PEG 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). This mPEG-OLA-PC can conjugate to primary amine groups in proteins or drugs. In mPEG-OLA-fluorescein model system, the OLA spacer was cleaved over 40% by 12 h and most fluorescein moieties were detached from mPEG by 84 h. G-CSF was pegylated with this activated mPEG-OLA-PC. Pegylated G-CSF was consisted of native, mono-, di-, and tri-pegylated species. When incubating in pH 4 buffer at 4℃ for 2 weeks, mPEG-OLA-G-CSF liberated mPEG by cleaving OLA spacer, resulting in the reduced fraction of multi-pegylated G-CSF with concomitantly increasing the fraction of native G-CSF. In vitro NFS60 cell proliferation assay revealed that mPEG-OLA-G-CSF retained similar activity to native G-CSF.
Advisors
Park, Tae-Gwanresearcher박태관researcher
Description
한국과학기술원 : 생물과학과,
Publisher
한국과학기술원
Issue Date
2001
Identifier
165535/325007 / 000993562
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생물과학과, 2001.2, [ vii, 45 p. ]

Keywords

Lactic acid; G-CSF; PEGylation; biodegradable; 락트산; 생분해성; 단백질 개질; 폴리에틸렌 글리콜 접합; p-nitrophenyl chloroformate

URI
http://hdl.handle.net/10203/27930
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=165535&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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