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Conjugation with Eight-Arm PEG Markedly Improves the In Vitro Activity and Prolongs the Blood Circulation of Staphylokinase
Qi, Fangbing1,2; Hu, Chunyang1; Yu, Weili1; Hu, Tao1
2018-02-01
发表期刊BIOCONJUGATE CHEMISTRY
ISSN1043-1802
卷号29期号:2页码:451-458
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.
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences
DOI10.1021/acs.bioconjchem.7b00770
收录类别SCI
语种英语
关键词[WOS]PEGYLATION ; PROTEIN ; PEPTIDE
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
WOS类目Biochemical Research Methods ; Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary ; Chemistry, Organic
项目资助者National Natural Science Foundation of China(81703445 ; 81700181)
WOS记录号WOS:000426144300026
引用统计
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/24006
专题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
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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.
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