Wu Wen-Hao, Guo Jianwen, Zhang Longshuai, Zhang Wen-Bin, Gao Weiping
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry & Physics of Ministry of Education, Center for Soft Matter Science and Engineering, College of Chemistry and Molecular Engineering, Peking University Beijing 100871 P. R. China
Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology Beijing 100081 P. R. China
RSC Chem Biol. 2022 Jun 9;3(7):815-829. doi: 10.1039/d1cb00246e. eCollection 2022 Jul 6.
Living organisms have evolved cyclic or multicyclic peptides and proteins with enhanced stability and high bioactivity superior to their linear counterparts for diverse purposes. Herein, we review recent progress in applying this concept to artificial peptides and proteins to exploit the functional benefits of these macrocycles. Not only have simple cyclic forms been prepared, numerous macrocycle variants, such as knots and links, have also been developed. The chemical tools and synthetic strategies are summarized for the biological synthesis of these macrocycles, demonstrating it as a powerful alternative to chemical synthesis. Its further application to therapeutic peptides/proteins has led to biomedicines with profoundly improved pharmaceutical performances. Finally, we present our perspectives on the field and its future developments.
生物进化出了环状或多环肽及蛋白质，它们具有更高的稳定性和生物活性，优于其线性对应物，可用于多种目的。在此，我们综述了将这一概念应用于人工肽和蛋白质以利用这些大环功能优势的最新进展。不仅制备了简单的环状形式，还开发了许多大环变体，如纽结和连接体。总结了这些大环生物合成的化学工具和合成策略，证明其是化学合成的有力替代方法。其在治疗性肽/蛋白质中的进一步应用已产生了具有显著改善药物性能的生物药物。最后，我们阐述了对该领域及其未来发展的观点。
