Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy.
Chem Soc Rev. 2020 Jun 7;49(11):3262-3277. doi: 10.1039/d0cs00102c. Epub 2020 Apr 7.
The art of transforming peptides into drug leads is still a dynamic and fertile field in medicinal chemistry and drug discovery. Peptidomimetics can respond to peptide limitations by displaying higher metabolic stability, good bioavailability and enhanced receptor affinity and selectivity. Various synthetic strategies have been developed over the years in order to modulate the conformational flexibility and the peptide character of peptidomimetic compounds. This tutorial review aims to outline useful tools towards peptidomimetic design, spanning from local modifications, global restrictions and the use of secondary structure mimetics. Selected successful examples of each approach are presented to document the relevance of peptidomimetics in drug discovery.
将肽转化为药物先导物的技术仍然是药物化学和药物发现领域中一个充满活力和富有成效的领域。肽模拟物可以通过显示更高的代谢稳定性、良好的生物利用度以及增强的受体亲和力和选择性来应对肽的局限性。多年来，已经开发了各种合成策略来调节肽模拟化合物的构象灵活性和肽性质。本综述旨在概述肽模拟设计的有用工具，包括局部修饰、全局限制和使用二级结构模拟物。本文介绍了每种方法的成功实例，以证明肽模拟物在药物发现中的相关性。
