Fan Cheng Kai, VanPatten Sonya, He Mingzhu, Al-Abed Yousef
Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
Curr Med Chem. 2022;29(42):6336-6358. doi: 10.2174/0929867329666220510214402.
For over 50 years of azapeptide synthetic techniques, developments have renewed the field of peptidomimetic therapeutics. Azapeptides are close surrogates of natural peptides: they contain a substitution of the amino acid α-carbon by a nitrogen atom. Goserelin (1989) and Atazanavir (2003) are two well-known, FDA-approved azapeptide-based drugs for the treatment of cancers and HIV infection, providing evidence for the successful clinical implementation of this class of therapeutic. This review highlights the azapeptides in recent medicinal chemistry applications and synthetic milestones. We describe the current techniques for azapeptide bond formation by introducing azapeptide coupling reagents and chain elongation methods both in solution and solid-phase strategies.
在过去50多年的氮杂肽合成技术发展中，该领域在拟肽疗法方面得以革新。氮杂肽是天然肽的紧密替代物：它们含有一个由氮原子取代氨基酸α-碳的结构。戈舍瑞林（1989年）和阿扎那韦（2003年）是两种著名的、经美国食品药品监督管理局批准的基于氮杂肽的药物，分别用于治疗癌症和HIV感染，为这类疗法的成功临床应用提供了证据。本综述重点介绍了氮杂肽在近期药物化学应用中的情况以及合成方面的里程碑事件。我们通过介绍氮杂肽偶联试剂以及溶液和固相策略中的链延长方法，描述了目前形成氮杂肽键的技术。
