Site-specific PEGylation of native disulfide bonds in therapeutic proteins
Author
Shaunak, Sunil
Godwin, Antony
Choi, Ji-Won
Balan, Sibu
Pedone, Elisa
Vijayarangam, Damotharan
Heidelberger, Sibylle
Teo, Ian
Zloh, Mire
Brocchini, Steve
Attention
2299/11452
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.