New platform technologies for the chemical synthesis of post-translationally modified proteins

在过去的十年中，批准用于临床的蛋白质药物数量激增，其中很大一部分具有翻译后修饰（PTMs）。这些修饰的蛋白质药物以混合物的形式生产和销售，这导致了在理解特定PTMs对活性的作用和获得候选药物临床批准方面的困难。该项目将通过开发新的合成方法和强大的新平台技术来获取纯形式的PTM蛋白，为这一问题提供根本性的解决方案。该技术的实用性将通过其在生物和医学应用的一系列PTM蛋白质的全化学合成中的应用来证明。

The last decade has seen an explosion in the number of protein drugs approved for use in the clinic, a large proportion of which possess post-translational modifications (PTMs). These modified protein drugs are produced and sold as mixtures which has led to difficulties in understanding the role of specific PTMs on activity and in gaining clinical approval for candidate drugs. This project will provide a fundamental solution to this problem through the development of novel synthetic methods and a powerful new platform technology for accessing PTM proteins in pure form. The utility of this technology will be demonstrated through its use in the total chemical synthesis of a range of PTM proteins for applications in biology and medicine.