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Conjugation of staphylokinase with the arabinogalactan-PEG conjugate: Study on the immunogenicity, in vitro bioactivity and pharmacokinetics.
- Source :
-
International Journal of Biological Macromolecules . Jun2019, Vol. 131, p896-904. 9p. - Publication Year :
- 2019
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BLOOD proteins
*BACTERIAL proteins
*ARABINOGALACTAN
*IMMUNOGLOBULIN G
*LARCHES
Subjects
Details
- Language :
- English
- ISSN :
- 01418130
- Volume :
- 131
- Database :
- Academic Search Index
- Journal :
- International Journal of Biological Macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 136153263
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2019.03.046