Comparison of bioactivities of monopegylated rhG-CSF with branched and linear mPEG
文献类型：期刊论文
| 作者 | Li, Xing-Qi1,2; Lei, Jian-Du1; Su, Zhi-Guo1; Ma, Guang-Hui1 |
| 刊名 | PROCESS BIOCHEMISTRY
 |
| 出版日期 | 2007-12-01 |
| 卷号 | 42期号:12页码:1625-1631 |
| 关键词 | synthesis branched mPEG rhG-CSF monopegylated rhG-CSF half-life time relative bioavailability |
| ISSN号 | 1359-5113 |
| 其他题名 | Process Biochem. |
| 中文摘要 | rhG-CSF (recombinant human granulocyte-colony stimulating factor) was chemically conjugated with branched mPEG (monomethoxyl polyethylene glycols), which was synthesized by a new method with the reaction between highly reactive carboxymethylated PEG succinimidy ester (SCM-PEG) and strongly nuclophilicitic amino group of lysine ethyl ester hydrochloride (lys-OEt 2HCl) in methylene chloride. The monopegylated rhG-CSF with branched mPEG (mono-B-pegylated rhG-CSF) was purified by one-step cationic exchange chromatography and characterized with HPSEC (high performance size exclusion chromatography), SDS-PAGE and MALDI-TOF MS. A monopegylated rhG-CSF with linear mPEG (mono-L-pegylated rhG-CSF) was also prepared to investigate the effect of structural difference on bioactivities. The comparison of mono-B-pegylated and mono-L-pegylated rhG-CSF was carried out on in vitro bioactivity, in vivo half-life time and Fr (relative bioavailability). The results showed that the in vitro relative bioactivity decreased to 54%, 61 % for mono-B-pegylated and mono-L-pegylated rhG-CSF, respectively. However, compared with the unmodified rhG-CSF, the mono-B-pegylated and mono-L-pegylated rhG-CSF prolonged plasma half-life time from 40 min to 190 min and 145 min, respectively. The Fr was 2.01 for the mono-B-pegylated rhG-CSF, while 1.32 for the mono-L-pegylated. These results suggested that the mono-B-pegylated rhG-CSF is more effective in improving pharmacokinetic performance than the mono-L-pegylated and unmodified rhG-CSF. (c) 2007 Elsevier Ltd. All rights reserved. |
| 英文摘要 | rhG-CSF (recombinant human granulocyte-colony stimulating factor) was chemically conjugated with branched mPEG (monomethoxyl polyethylene glycols), which was synthesized by a new method with the reaction between highly reactive carboxymethylated PEG succinimidy ester (SCM-PEG) and strongly nuclophilicitic amino group of lysine ethyl ester hydrochloride (lys-OEt 2HCl) in methylene chloride. The monopegylated rhG-CSF with branched mPEG (mono-B-pegylated rhG-CSF) was purified by one-step cationic exchange chromatography and characterized with HPSEC (high performance size exclusion chromatography), SDS-PAGE and MALDI-TOF MS. A monopegylated rhG-CSF with linear mPEG (mono-L-pegylated rhG-CSF) was also prepared to investigate the effect of structural difference on bioactivities. The comparison of mono-B-pegylated and mono-L-pegylated rhG-CSF was carried out on in vitro bioactivity, in vivo half-life time and Fr (relative bioavailability). The results showed that the in vitro relative bioactivity decreased to 54%, 61 % for mono-B-pegylated and mono-L-pegylated rhG-CSF, respectively. However, compared with the unmodified rhG-CSF, the mono-B-pegylated and mono-L-pegylated rhG-CSF prolonged plasma half-life time from 40 min to 190 min and 145 min, respectively. The Fr was 2.01 for the mono-B-pegylated rhG-CSF, while 1.32 for the mono-L-pegylated. These results suggested that the mono-B-pegylated rhG-CSF is more effective in improving pharmacokinetic performance than the mono-L-pegylated and unmodified rhG-CSF. (c) 2007 Elsevier Ltd. All rights reserved. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine ; Technology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Engineering, Chemical |
| 研究领域[WOS] | Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Engineering |
| 关键词[WOS] | INTERFERON ALPHA-2A ; POLYETHYLENE-GLYCOL ; HEPATITIS-C ; PEGYLATION ; PHARMACEUTICALS ; CONJUGATION |
| 收录类别 | SCI |
| 原文出处 | |
| 语种 | 英语 |
| WOS记录号 | WOS:000252289400009 |
| 公开日期 | 2013-10-15 |
| 版本 | 出版稿 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/3376]  |
| 专题 | 过程工程研究所_研究所（批量导入） |
| 作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100080, Peoples R China 2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xing-Qi,Lei, Jian-Du,Su, Zhi-Guo,et al. Comparison of bioactivities of monopegylated rhG-CSF with branched and linear mPEG[J]. PROCESS BIOCHEMISTRY,2007,42(12):1625-1631. |
| APA | Li, Xing-Qi,Lei, Jian-Du,Su, Zhi-Guo,&Ma, Guang-Hui.(2007).Comparison of bioactivities of monopegylated rhG-CSF with branched and linear mPEG.PROCESS BIOCHEMISTRY,42(12),1625-1631. |
| MLA | Li, Xing-Qi,et al."Comparison of bioactivities of monopegylated rhG-CSF with branched and linear mPEG".PROCESS BIOCHEMISTRY 42.12(2007):1625-1631. |
入库方式： OAI收割
来源：过程工程研究所
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