Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight

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	Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight
	Zhai, Yanqin 1,2; Zhao, Yongjiang 1,2; Lei, Jiandu 1; Su, Zhiguo 1; Ma, Guanghui 1
刊名	JOURNAL OF BIOTECHNOLOGY
	2009-07-15
卷号	142 期号:3-4 页码:259-266
关键词	Drug bioavailability Granulocyte colony stimulating factor (G-CSF) Serum half-life Site-specific PEGylation
ISSN号	0168-1656
通讯作者	Lei, JD
英文摘要	Recombinant human granulocyte colony stimulating factor (rhG-CSF) and its PEGylated product "mono-PEG20-GCSF" have already been widely used for treatment of all kinds of neutropenia. However, I he high required dosage of mono-PEG20-GCSF made it relatively expensive in clinical use. We postulated that an N-terminal site-specific PEGylated rhG-CSF with higher PEG Mw (PEG30 kDa) might be able to achieve longer circulation half-life while retaining its bioactivity, allowing the reduction of dosage for clinical use. rhG-CSF was PEGylated at the N-terminus by 5 kDa, 10 kDa, 20 kDa and 30 kDa methoxypoly(ethylene glycol)-propionaldehyde (niPEG-ALD), and the four PEGylates were compared with respect to reaction, separation, characterization and also in vivo/in vitro activity, results showed that the mPEG-ALD of higher Mw demonstrated better N-terminal site-specific selectivity. separation purity and yield. The production cost and in vitro activity of mono-PEG30-GCSF and rnono-PEG20-GCSF were almost the same, while mono-PEG30-GCSF showed longer in vivo circulation half-life and 60% higher drug bioavailability than mono-PEG20-GCSF Consequently, mono-PEG30-GCSF shall be administered at a lower dosage than mono-PEG20-GCSF while retaining the same therapeutic efficacy. (C) 2009 Elsevier B.V. All rights reserved.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biotechnology & Applied Microbiology
研究领域[WOS]	Biotechnology & Applied Microbiology
关键词[WOS]	COLONY-STIMULATING FACTOR ; ION-EXCHANGE CHROMATOGRAPHY ; ACUTE MYELOID-LEUKEMIA ; POLY(ETHYLENE GLYCOL) ; CLINICAL-APPLICATIONS ; INTERFERON ALPHA-2A ; DAILY FILGRASTIM ; PEGFILGRASTIM ; CHEMOTHERAPY ; PROTEINS
收录类别	SCI
语种	英语
WOS记录号	WOS:000268823400011
公开日期	2013-12-06
内容类型	期刊论文
版本	出版稿
源URL	[http://ir.ipe.ac.cn/handle/122111/6634]
专题	过程工程研究所_生化工程国家重点实验室
作者单位	1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhai, Yanqin,Zhao, Yongjiang,Lei, Jiandu,et al. Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight[J]. JOURNAL OF BIOTECHNOLOGY,2009,142(3-4):259-266.
APA	Zhai, Yanqin,Zhao, Yongjiang,Lei, Jiandu,Su, Zhiguo,&Ma, Guanghui.(2009).Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight.JOURNAL OF BIOTECHNOLOGY,142(3-4),259-266.
MLA	Zhai, Yanqin,et al."Enhanced circulation half-life of site-specific PEGylated rhG-CSF: Optimization of PEG molecular weight".JOURNAL OF BIOTECHNOLOGY 142.3-4(2009):259-266.