Site-specific PEGylation of native disulfide bonds in therapeutic proteins
Site-specific PEGylation of native disulfide bonds in therapeutic proteins
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DOI：
10.1038/nchembio786
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发表时间：
2006-06-01
影响因子：
14.8
通讯作者：
Brocchini, Steve
中科院分区：
文献类型：
--
作者：
Shaunak, Sunil;Godwin, Antony;Brocchini, Steve
治疗性蛋白中的天然二硫键对三级结构和生物活性至关重要，因此被认为不适合进行化学修饰（1,2）。我们发现，人干扰素α -2b和CD4（+）抗体片段中的天然二硫化物可以通过两个半胱氨酸硫原子的位点特异性双烷基化修饰，形成一个三碳聚乙二醇桥。聚乙二醇化蛋白的产率高，并保留三级结构和生物活性。
Native disulfide bonds in therapeutic proteins are crucial for tertiary structure and biological activity and are therefore considered unsuitable for chemical modification(1,2). 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.