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Updated: Aug 9, 2026

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
Site-specific PEGylation of native disulfide bonds in therapeutic proteins
Sunil Shaunak1, Antony Godwin, Ji-Won Choi
1Faculty of Medicine, Imperial College London, Hammersmith Hospital, Ducane Road, London W12 0NN, UK. s.shaunak@imperial.ac.uk
Abstract:
Native disulfide bonds in therapeutic proteins are crucial for tertiary structure and biological activity and are therefore considered unsuitable for chemical modification. We show that native disulfides in human interferon alpha-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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