Fine-tuning the conformations of cyclic peptides: a paradigm for optimising synthetic efficiency and biological activity

这项建议开发了一种策略，用于优化一类重要的药物分子的合成和性质，即环肽。这种分子作为治疗剂显示出很大的前景，但它们可能很难合成，它们的三维形状也很难控制。这个项目同时解决了这两个问题，通过利用一系列不寻常的氨基酸构建块，这些构建块具有各种形状和不同水平的构象灵活性。这一战略将使各种与治疗相关的环肽的开发成为可能，为了例证这一概念，将创建一组专门针对抗实体肿瘤活性的环肽。

This proposal develops a strategy for optimising the synthesis and properties of an important class of drug molecules known as cyclic peptides. Such molecules show great promise as therapeutic agents, but they can be very difficult to synthesise and their three-dimensional shapes can be difficult to control. This project simultaneously addresses both of these problems, by exploiting a series of unusual amino acid building blocks that have a variety of shapes and different levels of conformational flexibility. This strategy will enable the development of a wide variety of therapeutically-relevant cyclic peptides, and to exemplify this concept a panel of cyclic peptides will be created that are specifically targeted for activity against solid tumours.