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 (e.g., native chemical ligation and transition metal catalysis), biological (e.g., post-translational enzymatic modification and genetic code reprogramming), and supramolecular (e.g., mechanically interlocked, metal-directed folding and self-assembly via 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.

中文翻译：

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肽大环化策略的最新进展


近年来，由于其特殊的空间结构，基于肽的大环显示出巨大的前景，并引起了人们对多学科研究的极大兴趣，从针对耐药菌株的强效抗生素到具有新特性的功能性生物材料。除了传统的单环肽外，由于各种化学（例如天然化学连接和过渡金属催化）、生物学（例如翻译后酶修饰和遗传密码重编程）和超分子（例如机械互锁、金属定向折叠和自组装）的突破，许多迷人的多环和显着的高阶环状、球形和圆柱形肽系统已成为人们关注的焦点通过非共价相互作用）大环化策略是近几十年来开发的。在本教程综述中，调查和讨论了用于肽和拟肽物的各种最先进的大环化方法和技术，并深入了解了它们的实际优势和内在局限性。最后，讨论了综合技术方面、当前未解决的挑战以及该领域的前景。