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N-terminal mono-PEGylation of growth hormone antagonist: Correlation of PEG size and pharmacodynamic behavior
Wu, Ling1,4; Ho, Sa V.2; Wang, Wei3; Gao, Jianping1; Zhang, Guifeng1; Su, Zhiguo1; Hu, Tao1
2013-09-10
Source PublicationINTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume453Issue:2Pages:533-540
AbstractGrowth 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.
KeywordPegylation Growth Hormone Antagonist N-terminus Polyethylene Glycol Acromegaly
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Keyword40 KDA PEG-INTERFERON-ALPHA(2A) ; INDIVIDUAL POSITIONAL ISOMERS ; POLY(ETHYLENE GLYCOL) ; EXTRACELLULAR DOMAIN ; RECEPTOR ANTAGONISTS ; POLYETHYLENE GLYCOL ; PEGVISOMANT THERAPY ; PURIFICATION ; HEMOGLOBIN ; BINDING
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000323015800032
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/13531
Collection研究所(批量导入)
Affiliation1.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
Recommended Citation
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.
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