Disulfide bridging protein conjugation

在过去的20年里，基于蛋白质的药物在治疗严重的医学疾病中发挥着越来越重要的作用。它们现在是新药中增长最快的部门。它们从体内的快速清除导致它们被连接到聚乙二醇(PEG)，作为一种延长蛋白质在体内的循环时间和降低其毒性的手段。这种方法非常成功。然而，这些目前的聚乙二醇化技术受到严重限制，仅适用于资源丰富的国家的患者。因此，迫切需要创新和具有成本效益的生物技术，使资源贫乏国家的传染病患者能够更广泛地获得聚乙二醇化蛋白质。我们描述了一种解决这一问题的新生物技术，并说明了它在治疗丙型肝炎感染的干扰素-A2以及防止HIV-1细胞间传播的抗CD4抗体片段中的应用。

Over the last 20 years, protein based medicines have been acquiring an increasingly important role in the treatment of serious medical diseases. They are now the fastest growing sector of new medicines. Their rapid clearance from the body led to them being linked to poly(ethylene glycol) (PEG) as a means by which to prolong the protein's circulation time in the body and reduce its toxicity. This approach has been very successful. However, these current PEG technologies are severely limited and are only available to patients in resource rich countries. There is therefore an urgent need for innovative and cost-effective biotechnology that makes PEGylated proteins more widely available for patients with infectious diseases in resource poor countries. We describe a novel biotechnology that solves this problem, and illustrate its application to IFN-a2 for treating Hepatitis C infection, and to an anti-CD4 antibody fragment that prevents the cell-to-cell transmission of HIV-1.