PMID: 2813359

 

    Legend: Sugar

Title : Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells

Abstract :

1. 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
2. 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 )
3. In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO
4. EPO-bi, EPO-tetra, and the standard EPO had the same amino acid com position and immunoreactivity
5. 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.
6. 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
7. These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO