Structural analysis of the glycosylation of gene-activated erythropoietin (epoetin delta, Dynepo)
Abstract
Recently, a novel recombinant human erythropoietin (epoetin delta, Dynepo) has been marketed in the European Union for the treatment of chronic kidney disease, cancer patients receiving chemotherapy, and so forth. Epoetin delta is engineered in cultures of the human fibrosarcoma cell line HT-1080 by homologous recombination and "gene activation." Unlike recombinant erythropoietins produced in other mammalian cells, epoetin delta is supposed to have a human-type glycosylation profile. However, the isoelectric focusing profile of epoetin delta differs from that of endogenous erythropoietin (both urinary and plasmatic). In this work, structural and quantitative analysis of the O- and N-glycans of epoetin delta was performed and compared with glycosylation from recombinant erythropoietin produced in Chinese hamster ovary (CHO) cells. From the comparison, significant differences in the sialylation of O-glycans were found. Furthermore, the N-glycan analysis indicated a lower heterogeneity from epoetin delta when compared with its CHO homologue, being predominantly tetraantennary without N-acetyllactosamine repeats in the former. The sialic acid characterization revealed the absence of N-glycolylneuraminic acid. The overall sugar profiles of both glycoproteins appeared to be significantly different and could be useful for maintaining pharmaceutical quality control, detecting the misuse of erythropoietin in sports, and establishing new avenues to link glycosylation with biological ac…
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Epoetin delta produced in HT-1080 had better homogeneity of tetra-antennary glycans, higher sialic acid content, and no Neu5Gc compared to CHO-produced erythropoietin.
“Epoeitin delta produced in HT-1080 was found to have better homogeneity of its tetra-antennary glycans, higher sialic acid content and no Neu5Gc, compared to CHO-produced erythropoietin (Llop et al., 2008).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Llop et al., 2008
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Varki, A. (2017) · Glycobiology · doi:10.1093/glycob/cww086 · Cited by 2,635 · see citing works
“The size, number, branching and degree of sialylation of N-glycans can generate numerous glycoforms of a single polypeptide such as erythropoietin (629) (630) (631) (632) (633) (634) (635) (636) (637) (638) (639) (640) or GM-CSF (641) (642) (643) (644) .”
BackgroundTherapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
Jayo, R. G., Thaysen-Andersen, M., Lindenburg, P. W., Haselberg, R., Hankemeier, T., Ramautar, R., & Chen, D. D. Y. (2014) · Analytical Chemistry · doi:10.1021/ac5010212 · Cited by 54 · see citing works
De Masi, R., & Orlando, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137373 · Cited by 20 · see citing works
- Authors
- Llop, E., Gutiérrez-Gallego, R., Segura, J., Mallorquí, J., & Pascual, J. A.
- Affiliations
- Barcelona Biomedical Research Park (ES)
- Universitat Pompeu Fabra (ES)
- Venue
- Analytical Biochemistry
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 383
- Issue
- 2
- Pages
- 243-254
- ISSN
- 0003-2697 (ISSN-L)
- OpenAlex
- W2139198918
- Cited by
- 79
- References
- 0
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 1 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 6 · 2014: 6 · 2013: 12 · 2012: 4
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Analytical Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- World Anti-Doping Agency
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- recombinant human erythropoietin, gene activation, HT1080 cells, glycosylation, O-glycans, N-glycans, sialylation, sialic acid, N-glycolylneuraminic acid, N-acetyllactosamine, isoelectric focusing, pharmaceutical quality control
- MeSH terms
- Animals, Cricetulus, Erythropoietin, Glycoproteins, Glycosylation, Cricetinae, Humans, Isoelectric Focusing, Polysaccharides, Recombinant Proteins, Transcriptional Activation, CHO Cells, N-Acetylneuraminic Acid, Protein Isoforms
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