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

在过去的十年里，被批准用于临床的蛋白质药物的数量呈爆炸式增长，其中很大一部分具有翻译后修饰(PTM)。这些修饰的蛋白质药物是以混合物的形式生产和销售的，这导致难以了解特定的PTM对活性的作用，也难以获得候选药物的临床批准。这个项目将通过开发新的合成方法和一个强大的新平台技术来获得纯形式的PTM蛋白，从而为这个问题提供一个根本的解决方案。这项技术的用途将通过它在一系列用于生物和医学应用的PTM蛋白质的全化学合成中的使用来展示。

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.