Shaunak Sunil, Godwin Antony, Choi Ji-Won, Balan Sibu, Pedone Elisa, Vijayarangam Damotharan, Heidelberger Sibylle, Teo Ian, Zloh Mire, Brocchini Steve
Faculty of Medicine, Imperial College London, Hammersmith Hospital, Ducane Road, London W12 0NN, UK.
Nat Chem Biol. 2006 Jun;2(6):312-3. doi: 10.1038/nchembio786. Epub 2006 Apr 23.
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.
治疗性蛋白质中的天然二硫键对于三级结构和生物活性至关重要，因此被认为不适用于化学修饰。我们发现，人干扰素α-2b以及抗CD4(+)抗体片段中的天然二硫键可以通过两个半胱氨酸硫原子的位点特异性双烷基化进行修饰，以形成一个三碳聚乙二醇化桥。聚乙二醇化蛋白的产率很高，并且保留了三级结构和生物活性。
