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Phenyl Linker-Induced Dense PEG Conformation Improves the Efficacy of C-Terminally MonoPEGylated Staphylokinase
Xue, Xiaoying1,2; Li, Dongxia1; Yu, Jingkai1; Ma, Guanghui1; Su, Zhiguo1; Hu, Tao1
2013-02-01
Source PublicationBIOMACROMOLECULES
Volume14Issue:2Pages:331-341
AbstractPEGylation 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.
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
Indexed BySCI
Language英语
WOS KeywordSITE-SPECIFIC PEGYLATION ; HUMAN GROWTH-HORMONE ; RECOMBINANT STAPHYLOKINASE ; THROMBOLYTIC PROPERTIES ; POLY(ETHYLENE GLYCOL) ; DRUG-DELIVERY ; GENETIC-CODE ; X-RAY ; HEMOGLOBIN ; CONJUGATION
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry ; Polymer Science
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Organic ; Polymer Science
WOS IDWOS:000314908500006
Citation statistics
Cited Times:25[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/13559
Collection研究所(批量导入)
Affiliation1.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
Recommended Citation
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.
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