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Therapeutic proteins

Glycoengineered to last longer

Nature Reviews Drug Discovery volume 2, page 339 (2003)Cite this article

The crucial difference between rHuEPO and darbepoetin alfa that prolongs the activity of the latter is the attachment of two extra sialic-acid-containing N-linked carbohydrates to its polypeptide backbone. In a paper published online in Nature Biotechnology, Elliott and colleagues describe the method by which they manipulated the glycosylation pattern of rHuEPO to effect this structural change.

The rHuEPO polypeptide undergoes post-translational glycosylation at three specific asparagine (Asn) residues and one serine (Ser) residue. These residues are within the consensus sequence Asn–X–Ser/threonine (where X represents any amino acid other than proline), the conserved arrangement of amino acids to which carbohydrates preferentially bind. Hypothesizing that increasing the number of these glycosylation sites would increase the likelihood of carbohydrate attachment, Elliott et al. used in vitro mutagenesis to incorporate extra consensus sequences into the rHuEPO polypeptide.

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References

ORIGINAL RESEARCH PAPER

  1. Elliott, S. et al. Enhancement of therapeutic protein in vivo activities through glycoengineering. Nature Biotechnol. 3 March 2003 (doi: 10.1038/nbt799)

FURTHER READING

  1. Dwek, R. A., Butters, T. D., Platt, F. M. & Zitzmann, N. Targeting glycosylation as a therapeutic approach. Nature Rev. Drug Discov. 1, 65–75 (2002)

    Article  CAS  Google Scholar 

  2. Lindberg, J. Darbepoetin alfa: a new therapy for the management of anaemia associated with chronic kidney disease. Expert Opin. Biol. Ther. 2, 977–984 (2002)

    Article  CAS  Google Scholar 

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Authors
  1. Suzanne Farley
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Farley, S. Glycoengineered to last longer. Nat Rev Drug Discov 2, 339 (2003). https://doi.org/10.1038/nrd1096

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