Fang Pengyuan, Pang Wing-Ka, Xuan Shouhu, Chan Wai-Lun, Leung Ken Cham-Fai
Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou 350207, Fujian, P. R. China.
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR, P. R. China.
Chem Soc Rev. 2024 Dec 9;53(24):11725-11771. doi: 10.1039/d3cs01066j.
Recently, owing to their special spatial structures, peptide-based macrocycles have shown tremendous promise and aroused great interest in multidisciplinary research ranging from potent antibiotics against resistant strains to functional biomaterials with novel properties. Besides traditional monocyclic peptides, many fascinating polycyclic and remarkable higher-order cyclic, spherical and cylindric peptidic systems have come into the limelight owing to breakthroughs in various chemical (, native chemical ligation and transition metal catalysis), biological (, post-translational enzymatic modification and genetic code reprogramming), and supramolecular (, mechanically interlocked, metal-directed folding and self-assembly noncovalent interactions) macrocyclization strategies developed in recent decades. In this tutorial review, diverse state-of-the-art macrocyclization methodologies and techniques for peptides and peptidomimetics are surveyed and discussed, with insights into their practical advantages and intrinsic limitations. Finally, the synthetic-technical aspects, current unresolved challenges, and outlook of this field are discussed.
最近，基于肽的大环化合物因其特殊的空间结构，在多学科研究中展现出巨大的潜力，并引起了广泛关注，其应用范围涵盖从对抗耐药菌株的强效抗生素到具有新颖特性的功能性生物材料等领域。除了传统的单环肽之外，由于近几十年来在各种化学（如天然化学连接和过渡金属催化）、生物学（如翻译后酶修饰和遗传密码重编程）以及超分子（如机械互锁、金属导向折叠和自组装非共价相互作用）大环化策略方面取得的突破，许多引人入胜的多环以及卓越的高阶环状、球形和圆柱形肽类体系也备受瞩目。在本教程综述中，我们对用于肽和肽模拟物的各种先进大环化方法和技术进行了调查和讨论，并深入探讨了它们的实际优势和内在局限性。最后，我们讨论了该领域的合成技术方面、当前尚未解决的挑战以及前景。
