N-terminal mono-PEGylation of growth hormone antagonist: Correlation of PEG size and pharmacodynamic behavior
文献类型：期刊论文
| 作者 | Wu, Ling1,4; Ho, Sa V.2; Wang, Wei3; Gao, Jianping1; Zhang, Guifeng1; Su, Zhiguo1; Hu, Tao1 |
| 刊名 | INTERNATIONAL JOURNAL OF PHARMACEUTICS
 |
| 出版日期 | 2013-09-10 |
| 卷号 | 453期号:2页码:533-540 |
| 关键词 | PEGylation Growth hormone antagonist N-terminus Polyethylene glycol Acromegaly |
| 英文摘要 | Growth hormone antagonist (GHA), an analog of growth hormone (GH), can inhibit GH action and treat acromegaly. However, GHA suffers from a short plasma half-life of 15-20 min that has limited its clinical application. PEGylation, conjugation with polyethylene glycol (PEG), can increase the plasma half-life of GHA. Single PEG attachment (mono-PEGylation) at N-terminus of GHA has the advantages of product homogeneity and minimization of the bioactivity loss. Conjugation of large PEG molecule may increase the plasma half-life but could potentially decrease the bioactivity of GHA, due to the steric shielding effect of PEG. Thus, N-terminal mono-PEGylation of GHA with 20 kDa and 40 kDa PEG were used to look for a balance of the two competing factors. Sedimentation velocity analysis suggested that 40 kDa PEG was more efficient than 20 kDa PEG to elongate the molecular shape of the conjugate. As reflected by marginal suppression of insulin-like growth factor I (IGF-I), GHA conjugated with 40 kDa PEG was statistically indistinguishable from the saline solution that could not inhibit GH action. In contrast, GHA conjugated with 20 kDa PEG can apparently inhibit GH action, as reflected by IGF-I suppression of 30-43%. Thus, our work demonstrated the effective therapeutic potency of N-terminally mono-PEGylated GHA. (C) 2013 Elsevier B.V. All rights reserved. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Pharmacology & Pharmacy |
| 研究领域[WOS] | Pharmacology & Pharmacy |
| 关键词[WOS] | 40 KDA PEG-INTERFERON-ALPHA(2A) ; INDIVIDUAL POSITIONAL ISOMERS ; POLY(ETHYLENE GLYCOL) ; EXTRACELLULAR DOMAIN ; RECEPTOR ANTAGONISTS ; POLYETHYLENE GLYCOL ; PEGVISOMANT THERAPY ; PURIFICATION ; HEMOGLOBIN ; BINDING |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000323015800032 |
| 公开日期 | 2015-05-27 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/13531]  |
| 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 100190, Peoples R China 2.Pfizer Inc, Biotherapeut R&D, Andover, MA 01810 USA 3.Pfizer Inc, Biotherapeut R&D, Chesterfield, MO 63017 USA 4.Univ Chinese Acad Sci, Beijing 100190, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Ling,Ho, Sa V.,Wang, Wei,et al. N-terminal mono-PEGylation of growth hormone antagonist: Correlation of PEG size and pharmacodynamic behavior[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2013,453(2):533-540. |
| APA | Wu, Ling.,Ho, Sa V..,Wang, Wei.,Gao, Jianping.,Zhang, Guifeng.,...&Hu, Tao.(2013).N-terminal mono-PEGylation of growth hormone antagonist: Correlation of PEG size and pharmacodynamic behavior.INTERNATIONAL JOURNAL OF PHARMACEUTICS,453(2),533-540. |
| MLA | Wu, Ling,et al."N-terminal mono-PEGylation of growth hormone antagonist: Correlation of PEG size and pharmacodynamic behavior".INTERNATIONAL JOURNAL OF PHARMACEUTICS 453.2(2013):533-540. |
入库方式： OAI收割
来源：过程工程研究所
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