Site-specific PEGylation of native disulfide bonds in therapeutic proteins

Sunil Shaunak; Antony Godwin; Ji-Won Choi; Sibu Balan; Elisa Pedone; Damotharan Vijayarangam; Sibylle Heidelberger; Ian Teo; Mire Zloh; Steve Brocchini

doi:10.1038/nchembio786

Site-specific PEGylation of native disulfide bonds in therapeutic proteins

Sunil Shaunak, Antony Godwin, Ji-Won Choi, Sibu Balan, Elisa Pedone, Damotharan Vijayarangam, Sibylle Heidelberger, Ian Teo, Mire Zloh, Steve Brocchini

School of Life and Medical Sciences

Research output: Contribution to journal › Article › peer-review

205 Citations (Scopus)

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.

Original language	English
Pages (from-to)	312-3
Number of pages	2
Journal	Nature Chemical Biology
Volume	2
Issue number	6
DOIs	https://doi.org/10.1038/nchembio786
Publication status	Published - 2006

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10.1038/nchembio786

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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.",

author = "Sunil Shaunak and Antony Godwin and Ji-Won Choi and Sibu Balan and Elisa Pedone and Damotharan Vijayarangam and Sibylle Heidelberger and Ian Teo and Mire Zloh and Steve Brocchini",

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T1 - Site-specific PEGylation of native disulfide bonds in therapeutic proteins

AU - Shaunak, Sunil

AU - Godwin, Antony

AU - Choi, Ji-Won

AU - Balan, Sibu

AU - Pedone, Elisa

AU - Vijayarangam, Damotharan

AU - Heidelberger, Sibylle

AU - Teo, Ian

AU - Zloh, Mire

AU - Brocchini, Steve

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - 10.1038/nchembio786

DO - 10.1038/nchembio786

M3 - Article

C2 - 16633351

SN - 1552-4450

VL - 2

SP - 312

EP - 313

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 6

ER -

Site-specific PEGylation of native disulfide bonds in therapeutic proteins

Abstract

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