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Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; October 1989, Vol. 86 Issue: 20 p7819-7822, 4p
- Publication Year :
- 1989
-
Abstract
- Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO.
Details
- Language :
- English
- ISSN :
- 00278424 and 10916490
- Volume :
- 86
- Issue :
- 20
- Database :
- Supplemental Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Periodical
- Accession number :
- ejs60440024
- Full Text :
- https://doi.org/10.1073/pnas.86.20.7819