Abstract
Native disulfide bonds in therapeutic proteins are crucial for tertiary structure and biological activity and are therefore considered unsuitable for chemical modification1,2. We show that native disulfides in human interferon α-2b and in a fragment of an antibody to CD4+ can be modified by site-specific bisalkylation of the two cysteine sulfur atoms to form a three-carbon PEGylated bridge. The yield of PEGylated protein is high, and tertiary structure and biological activity are retained.
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Acknowledgements
The authors thank the National Institute for Biological Standards and Control (UK) for Q4120/ADP318 antibody. This work was supported by the Wellcome Trust (068309) and BBSRC-UK (BB/D003636/1).
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S.S., A.G., J.-W.C. and S.B. are inventors on a patent that has been assigned to a new university spinout company called PolyTherics. The Wellcome Trust, Imperial College London, University College London, School of Pharmacy London, S.S. and S.B. hold equity in this company.
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Shaunak, S., Godwin, A., Choi, JW. et al. Site-specific PEGylation of native disulfide bonds in therapeutic proteins. Nat Chem Biol 2, 312–313 (2006). https://doi.org/10.1038/nchembio786
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DOI: https://doi.org/10.1038/nchembio786
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