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Conjugation of staphylokinase with the arabinogalactan-PEG conjugate: Study on the immunogenicity, in vitro bioactivity and pharmacokinetics
Qi, Fangbing1,2; Qi, Jinming1,2; Hu, Chunyang1; Shen, Lijuan1; Yu, Weili1; Hu, Tao1
2019-06-15
Source PublicationINTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
ISSN0141-8130
Volume131Pages:896-904
AbstractStaphylokinase (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.
KeywordStaphylokinase Arabinogalactan Immunogenicity Pharmacokinetic PEG linker in vitro activity
DOI10.1016/j.ijbiomac.2019.03.046
Language英语
WOS KeywordBETA-LACTOGLOBULIN ; PROTEINS ; ANTIPLATELET ; PEGYLATION
Funding ProjectNational Natural Science Foundation of China[81703445] ; National Natural Science Foundation of China[81700181]
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry ; Polymer Science
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Applied ; Polymer Science
Funding OrganizationNational Natural Science Foundation of China
WOS IDWOS:000468252800098
PublisherELSEVIER SCIENCE BV
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/28152
Collection中国科学院过程工程研究所
Corresponding AuthorYu, Weili; Hu, Tao
Affiliation1.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
Recommended Citation
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.
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