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

本提案开发了一种策略，用于优化被称为环肽的一类重要药物分子的合成和性质。这类分子作为治疗药物大有希望，但它们很难合成，而且它们的三维形状也很难控制。该项目同时解决了这两个问题，通过开发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。这一策略将使各种治疗相关的环肽的发展成为可能，并举例说明这一概念，将创建一个专门针对实体肿瘤活性的环肽面板。

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.