Abstract
Glycoproteins are an important class of naturally occurring biomolecules which play a pivotal role in many biological processes. They are biosynthesized as complex mixtures of glycoforms through post-translational protein glycosylation. This fact, together with the challenges associated with producing them in homogeneous form, has hampered detailed structure-function studies of glycoproteins as well as their full exploitation as potential therapeutic agents. By contrast, chemical synthesis offers the unique opportunity to gain access to homogeneous glycoprotein samples for rigorous biological evaluation. Herein, we review recent methods for the assembly of complex glycopeptides and glycoproteins and present several examples from our laboratory towards the total chemical synthesis of clinically relevant glycosylated proteins that have enabled synthetic access to full-length homogeneous glycoproteins.
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Acknowledgements
We thank the National Institutes of Health, William and Alice Goodwin and the Commonwealth Foundation for Cancer Research for generous financial support. AF-T gratefully acknowledges the European Commission (Marie Curie International Outgoing Fellowship) for funding. We acknowledge our colleagues of the Danishefsky laboratory whose work is presented in this manuscript. We thank Professors Yasuhiro Kajihara and Carlo Unverzagt for provocative exchanges and, particularly, for citing precedence on the feasibility of obtaining informative mass spectra of related EPO structures. We thank Rebecca Wilson for assistance in the preparation of the manuscript.
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Fernández-Tejada, A., Brailsford, J., Zhang, Q., Shieh, JH., Moore, M.A.S., Danishefsky, S.J. (2014). Total Synthesis of Glycosylated Proteins. In: Liu, L. (eds) Protein Ligation and Total Synthesis I. Topics in Current Chemistry, vol 362. Springer, Cham. https://doi.org/10.1007/128_2014_622
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DOI: https://doi.org/10.1007/128_2014_622
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