Preparation, characterization and in vitro bioactivity of N-terminally PEGylated staphylokinase dimers
文献类型:期刊论文
作者 | Liu, Ruyan1,2; Li, Dongxia1; Wang, Jun1,2; Qiu, Rui1,3; Lin, Qixun3; Zhang, Guifeng1; Ma, Guanghui1; Su, Zhiguo1; Hu, Tao1 |
刊名 | PROCESS BIOCHEMISTRY
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出版日期 | 2012 |
卷号 | 47期号:1页码:41-46 |
关键词 | Staphylokinase Dimerization PEGylation Bioactivity Steric hindrance |
ISSN号 | 1359-5113 |
通讯作者 | Hu, T |
英文摘要 | PEGylation can improve the therapeutic efficacy of proteins by increasing serum half-life of proteins and reducing immunogenicity and antigenicity. However, PEGylation results in a substantial loss of the bioactivity of proteins due to the steric hindrance of polyethylene glycol (PEG). Dimerization of the proteins is an efficient approach to increase the bioactivity of the PEG-protein conjugates. Here, staphylokinase (SAK) was used due to its therapeutic potential for coronary thrombolysis. SAK dimers (dSAK) were prepared by engineering cysteine residue at the C-terminus of SAK and dimerization of the cysteine residue with 1,4-bismaleimidobutane. PEG aldehyde was used for site-specific PEGylation of dSAK at one of its two N-termini. Structural analysis indicated that dimerization of SAK can decrease the steric hindrance of PEG and increase the binding affinity of PEG-SAK to plasminogen. Dimerization of SAK increased the relative bioactivity of PEG-SAK from 39.0% to 62.0%. Therefore, site-specifically PEGylated dSAK at one of its two N-termini has higher bioactivity than the N-terminal PEGylated SAK. (C) 2011 Elsevier Ltd. All rights reserved. |
WOS标题词 | Science & Technology ; Life Sciences & Biomedicine ; Technology |
类目[WOS] | Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Engineering, Chemical |
研究领域[WOS] | Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Engineering |
关键词[WOS] | POLYETHYLENE-GLYCOL ; PROTEIN PEGYLATION ; HEMOGLOBIN ; PEPTIDE |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000300133000006 |
公开日期 | 2013-10-28 |
版本 | 出版稿 |
源URL | [http://ir.ipe.ac.cn/handle/122111/4308] ![]() |
专题 | 过程工程研究所_生化工程国家重点实验室 |
作者单位 | 1.Chinese Acad Sci, Natl Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Grad Sch, Beijing 100190, Peoples R China 3.Fujian Agr & Forestry Univ, Coll Food Sci, Fuzhou 350002, Peoples R China |
推荐引用方式 GB/T 7714 | Liu, Ruyan,Li, Dongxia,Wang, Jun,et al. Preparation, characterization and in vitro bioactivity of N-terminally PEGylated staphylokinase dimers[J]. PROCESS BIOCHEMISTRY,2012,47(1):41-46. |
APA | Liu, Ruyan.,Li, Dongxia.,Wang, Jun.,Qiu, Rui.,Lin, Qixun.,...&Hu, Tao.(2012).Preparation, characterization and in vitro bioactivity of N-terminally PEGylated staphylokinase dimers.PROCESS BIOCHEMISTRY,47(1),41-46. |
MLA | Liu, Ruyan,et al."Preparation, characterization and in vitro bioactivity of N-terminally PEGylated staphylokinase dimers".PROCESS BIOCHEMISTRY 47.1(2012):41-46. |
入库方式: OAI收割
来源:过程工程研究所
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