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

该提案开发了一种策略，用于优化一类重要的药物分子（称为环肽）的合成和性质。这些分子作为治疗剂显示出巨大的前景，但它们可能非常难以合成，并且它们的三维形状可能难以控制。该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，具有各种形状和不同水平的构象灵活性。该策略将能够开发各种各样的治疗相关的环肽，并且为了证实这一概念，将创建一组环肽，其特异性靶向针对实体瘤的活性。

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.