Conjugation with Eight-Arm PEG Markedly Improves the In Vitro Activity and Prolongs the Blood Circulation of Staphylokinase
文献类型：期刊论文
| 作者 | Qi, Fangbing1,2; Hu, Chunyang1; Yu, Weili1; Hu, Tao1 |
| 刊名 | BIOCONJUGATE CHEMISTRY
 |
| 出版日期 | 2018-02-01 |
| 卷号 | 29期号:2页码:451-458 |
| ISSN号 | 1043-1802 |
| DOI | 10.1021/acs.bioconjchem.7b00770 |
| 文献子类 | Article |
| 英文摘要 | Staphylokinase (SAK) is a profibrinolytic protein and can be used for therapy of acute myocardial infarction and coronary thrombosis. However, SAK suffers from a short serum half-life time (similar to 6 min) that limits its clinical application. PEGylation prolongs the half-life time of SAK, whereas significantly decreases the bioactivity of SAK for the steric shielding effect of PEG. To improve the bioactivity and prolong the half-life time of SAK, 8-arm PEG maleimide (8-arm PEG) was used for conjugation of multiple SAK molecules in one entity. C terminus of SAK was engineered with cysteine residue, followed by reaction with the maleimide moieties of 8-arm PEG to obtain the conjugate (SAKp-PEG). Conjugation with 8-arm PEG retained the secondary structure of SAK, slightly perturbed the tertiary structure of SAK and essentially maintained its in vitro bioactivity by the multivalence of SAK. Conjugation with 8-arm PEG increased the hydrodynamic volume and thus significantly prolonged the half-life time of SAK. SAKp-PEG elicited a 1.4-fold increase in the SAK-specific IgG titers as compared with SAK, and rendered no apparent toxicity to the cardiac, liver and renal functions of mice. Thus, multiple conjugation of a protein with 8-arm PEG was an effective strategy to develop a long-acting protein drug with improved bioactivity and prolonged blood circulation. |
| WOS关键词 | PEGYLATION ; PROTEIN ; PEPTIDE |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000426144300026 |
| 资助机构 | National Natural Science Foundation of China(81703445 ; 81700181) |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/24006]  |
| 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, Inst Proc Engn, State Key Lab Biochem 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 | Qi, Fangbing,Hu, Chunyang,Yu, Weili,et al. Conjugation with Eight-Arm PEG Markedly Improves the In Vitro Activity and Prolongs the Blood Circulation of Staphylokinase[J]. BIOCONJUGATE CHEMISTRY,2018,29(2):451-458. |
| APA | Qi, Fangbing,Hu, Chunyang,Yu, Weili,&Hu, Tao.(2018).Conjugation with Eight-Arm PEG Markedly Improves the In Vitro Activity and Prolongs the Blood Circulation of Staphylokinase.BIOCONJUGATE CHEMISTRY,29(2),451-458. |
| MLA | Qi, Fangbing,et al."Conjugation with Eight-Arm PEG Markedly Improves the In Vitro Activity and Prolongs the Blood Circulation of Staphylokinase".BIOCONJUGATE CHEMISTRY 29.2(2018):451-458. |
入库方式： OAI收割
来源：过程工程研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。