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Post-translational modifications in the context of therapeutic proteins

Nature Biotechnology volume 24, pages 1241–1252 (2006)Cite this article

Abstract

The majority of protein-based biopharmaceuticals approved or in clinical trials bear some form of post-translational modification (PTM), which can profoundly affect protein properties relevant to their therapeutic application. Whereas glycosylation represents the most common modification, additional PTMs, including carboxylation, hydroxylation, sulfation and amidation, are characteristic of some products. The relationship between structure and function is understood for many PTMs but remains incomplete for others, particularly in the case of complex PTMs, such as glycosylation. A better understanding of such structural-functional relationships will facilitate the development of second-generation products displaying a PTM profile engineered to optimize therapeutic usefulness.

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Figure 1: Overview of the biosynthesis of protein N-linked glycan side chains.
Figure 2

Michelle Montoya

Figure 3
Figure 4: Protein carboxylation.

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Acknowledgements

We thank Kevin Moore of the Oklahoma Medical Research Foundation and Chiranjib Chakraborty, National Sun Yat-sen University (Kaohsiung; Taiwan) for their help with portions of the manuscript, and Darrell Stafford of the University of North Carolina (Chapel Hill) for his contributions of text and a figure for the carboxylation section.

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  1. Industrial Biochemistry Program, University of Limerick, Castletroy, Limerick City, Ireland

    Gary Walsh

  2. The Division of Immunity & Infection, University of Birmingham B15 2TT, United Kingdom

    Roy Jefferis

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Correspondence to Gary Walsh.

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Walsh, G., Jefferis, R. Post-translational modifications in the context of therapeutic proteins. Nat Biotechnol 24, 1241–1252 (2006). https://doi.org/10.1038/nbt1252

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