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Phenyl Linker-Induced Dense PEG Conformation Improves the Efficacy of C-Terminally MonoPEGylated Staphylokinase

文献类型：期刊论文

作者Xue, Xiaoying1,2; Li, Dongxia1; Yu, Jingkai1; Ma, Guanghui1; Su, Zhiguo1; Hu, Tao1
刊名BIOMACROMOLECULES
出版日期2013-02-01
卷号14期号:2页码:331-341
英文摘要PEGylation can improve the protein efficacy by prolonging serum half-life and reducing proteolytic sensitivity and immunogenicity. However, PEGylation may decrease the bioactivity of a protein by interfering with binding of its substrate or receptors. Here, staphylokinase (SAK), a thrombolysis agent for therapy of myocardial infarction, was mono-PEGylated at the C-terminus of SAK far from its bioactive domain. Phenyl, propyl, and amyl moieties were used as linkers between SAK and polyethylene glycol (PEG), respectively. Flexible propyl and amyl linkers lead to loose conformation. In contrast, rigid and hydrophobic phenyl linker induces dense PEG conformation that can extensively shield most domains adjacent to C-terminus (e.g., the antigen epitopes and proteolytic sites) of SAK and inefficiently shield its bioactive domain. As compared with loose PEG conformation, dense PEG conformation is more efficient to maintain the bioactivity, increase the plasma half-life, and decrease the proteolytic sensitivity and immunogenicity of the PEGylated SAK.
WOS标题词Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences
类目[WOS]Biochemistry & Molecular Biology ; Chemistry, Organic ; Polymer Science
研究领域[WOS]Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
关键词[WOS]SITE-SPECIFIC PEGYLATION ; HUMAN GROWTH-HORMONE ; RECOMBINANT STAPHYLOKINASE ; THROMBOLYTIC PROPERTIES ; POLY(ETHYLENE GLYCOL) ; DRUG-DELIVERY ; GENETIC-CODE ; X-RAY ; HEMOGLOBIN ; CONJUGATION
收录类别SCI
语种英语
WOS记录号WOS:000314908500006
公开日期2015-05-27
源URL[http://ir.ipe.ac.cn/handle/122111/13559]  
专题过程工程研究所_研究所（批量导入）
作者单位1.Chinese Acad Sci, Natl Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100190, Peoples R China
推荐引用方式
GB/T 7714		 Xue, Xiaoying,Li, Dongxia,Yu, Jingkai,et al. Phenyl Linker-Induced Dense PEG Conformation Improves the Efficacy of C-Terminally MonoPEGylated Staphylokinase[J]. BIOMACROMOLECULES,2013,14(2):331-341.
APA Xue, Xiaoying,Li, Dongxia,Yu, Jingkai,Ma, Guanghui,Su, Zhiguo,&Hu, Tao.(2013).Phenyl Linker-Induced Dense PEG Conformation Improves the Efficacy of C-Terminally MonoPEGylated Staphylokinase.BIOMACROMOLECULES,14(2),331-341.
MLA Xue, Xiaoying,et al."Phenyl Linker-Induced Dense PEG Conformation Improves the Efficacy of C-Terminally MonoPEGylated Staphylokinase".BIOMACROMOLECULES 14.2(2013):331-341.

入库方式： OAI收割

来源：过程工程研究所

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