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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 Publication | BIOMACROMOLECULES
 |
| Volume | 14Issue:2Pages:331-341 |
| Abstract | 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. |
| Subtype | Article |
| WOS Headings | Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences |
| Indexed By | SCI |
| Language | 英语 |
| WOS Keyword | SITE-SPECIFIC PEGYLATION ; HUMAN GROWTH-HORMONE ; RECOMBINANT STAPHYLOKINASE ; THROMBOLYTIC PROPERTIES ; POLY(ETHYLENE GLYCOL) ; DRUG-DELIVERY ; GENETIC-CODE ; X-RAY ; HEMOGLOBIN ; CONJUGATION |
| WOS Research Area | Biochemistry & Molecular Biology ; Chemistry ; Polymer Science |
| WOS Subject | Biochemistry & Molecular Biology ; Chemistry, Organic ; Polymer Science |
| WOS ID | WOS:000314908500006 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ipe.ac.cn/handle/122111/13559 |
| Collection | 研究所（批量导入） |
| Affiliation | 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 |
| 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. |
| Files in This Item: | ||||||
| File Name/Size | DocType | Version | Access | License | ||
| Phenyl Linker-Induce（2747KB） | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | Application Full Text | |
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