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Conjugation of staphylokinase with the arabinogalactan-PEG conjugate: Study on the immunogenicity, in vitro bioactivity and pharmacokinetics

文献类型:期刊论文

作者Qi, Fangbing1,2; Qi, Jinming1,2; Hu, Chunyang1; Shen, Lijuan1; Yu, Weili1; Hu, Tao1
刊名INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
出版日期2019-06-15
卷号131页码:896-904
关键词Staphylokinase Arabinogalactan Immunogenicity Pharmacokinetic PEG linker in vitro activity
ISSN号0141-8130
DOI10.1016/j.ijbiomac.2019.03.046
英文摘要Staphylokinase (SAK) is a bacterial protein with profibrinolytic activity. However, SAK suffers from short serum half-life and high immunogenicity. PEGylation with high Mw (20 kDa or 40 kDa) could decrease the immunogenicity and prolong the serum half-life of the proteins. However, the PEGylated protein could induce the anti-PEG antibodies and its bioactivity was significantly decreased. Arabinogalactan (AG) is a health-promoting substance with numerous biological activities. Conjugation of AG is an alternative strategy to solve the above-mentioned problems. However, conjugation with AG significantly decreased the bioactivity of a protein by shielding the bioactive domain. Here, AG conjugation and PEGylation were combined to improve the therapeutic efficacy of SAK. PEG with low Mw (2 kDa or 5 kDa) acted as a linker to conjugate AG from Larix. As compared with SAK-AG (22.3%), the conjugates (SAK-P2K-AG and SAK-P5K-AG) largely maintained the bioactivity of SAK (73.8% and 62.9%). The two conjugates both showed an 8-fold decrease in the SAK-specific IgG titers and a prolonged serum half-life. Moreover, the conjugates did not render any apparent toxicity to the heart, liver and renal functions of mice. Thus, our conjugation strategy is promising for the development of an effective long-acting therapeutic protein. (C) 2019 Elsevier B.V. All rights reserved.
WOS关键词BETA-LACTOGLOBULIN ; PROTEINS ; ANTIPLATELET ; PEGYLATION
资助项目National Natural Science Foundation of China[81703445] ; National Natural Science Foundation of China[81700181]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
语种英语
WOS记录号WOS:000468252800098
出版者ELSEVIER SCIENCE BV
资助机构National Natural Science Foundation of China
源URL[http://ir.ipe.ac.cn/handle/122111/28152]  
专题中国科学院过程工程研究所
通讯作者Yu, Weili; Hu, Tao
作者单位1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, 1 Bei Er Tiao St, 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,Qi, Jinming,Hu, Chunyang,et al. Conjugation of staphylokinase with the arabinogalactan-PEG conjugate: Study on the immunogenicity, in vitro bioactivity and pharmacokinetics[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2019,131:896-904.
APA Qi, Fangbing,Qi, Jinming,Hu, Chunyang,Shen, Lijuan,Yu, Weili,&Hu, Tao.(2019).Conjugation of staphylokinase with the arabinogalactan-PEG conjugate: Study on the immunogenicity, in vitro bioactivity and pharmacokinetics.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,131,896-904.
MLA Qi, Fangbing,et al."Conjugation of staphylokinase with the arabinogalactan-PEG conjugate: Study on the immunogenicity, in vitro bioactivity and pharmacokinetics".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 131(2019):896-904.

入库方式: OAI收割

来源:过程工程研究所

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