Erythropoietin biological activities

Erythropoiesis-stimulating agents Agents developed by recombinant DNA technology that have the same biologic activity as endogenous erythropoietin to stimulate erythropoiesis (red blood cell production) in the bone marrow. 

Yuen, C.T., Stoning, P.L., Tiplady, R.J. et al. (2003) Relationships between the A-glycan structures and biological activities of recombinant human erythropoietins produced using different culture conditions and purification procedures. British Journal of Haematology, 121 (3), 511-526. 

Mammalian cell culture is more technically complex and more expensive than microbial cell fermentation. It is, therefore, usually only used in the manufacture of therapeutic proteins that show extensive and essential post-translational modifications. In practice, this usually refers to glycosylation and the use of animal cell culture would be appropriate where the carbohydrate content and pattern is essential either to the protein s biological activity, stability or serum half-life. Therapeutic proteins falling into this category include erythropoietin (Chapter 6), the gonadotrophins (Chapter 8), some cytokines (Chapters 4-7) and intact monoclonal antibodies (Chapter 10). 

Cai P, Smith D, Katz B, Pearce C, Venables D, Houck D (1998) Destruxin-A4 Chlorohy-drin, a Novel Destruxin from the Fungus OS-F68576 Isolation, Structure Determination, and Biological Activity as an Inducer of Erythropoietin. J Nat Prod 61 290... 

The challenge of FOPs demonstrating similar quality, safety, and efficacy to the innovator product relates to the poor predictability of physicochemical characteristics and biologic activity. For example, there are several different interferon-a and erythropoietin a and P products currently on the market. These variants are characterized by differences in sequence, glycosylation pattern, and in vitro measures of specific activity however, their clinical safety and efficacy profiles are considered similar [20],... 

Goto, C., Akai, K., Murakami, A., Hashimoto, C., Tsuda, E., Ueda, M., Kawanishi, G., Takahashi, N., Ishimoto, A., Chiba, H., and Sasaki, R. (1988). Production of recombinant human erythropoietin in mammalian cells host-cell dependency of biological activity of the cloned glycoprotein. Bio/Technology 6, 67 71. 

Erythropoietin (EPO) is a naturally occurring protein responsible for red blood cell production. A 20mer peptide mimic of this natural protein has been synthesized in 8 h by use of microwave SPPS. Purity was higher than that obtained in 5 days by conventionally synthesis [33] and the biological activity was reported to be equal to that of the conventionally synthesized material, as shown in Fig. 20.16. 

Takeuchi, M. et al. Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells. Proc Natl Acad Sci USA, 86, 7819, 1989. 

It would be premature to state that the analysed product is pure erythropoietin there are some factors demonstrating even a less advanced degree of purification, but the technical procedure described above allows a purification with a minimal loss of biological activity up to this stage and an objective way to characterise the erythropoietin. 

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