Zhu Zirui, Poweleit Andrew, Girard Louisa, Sun Wenjun, Ma Haowei, Nice Edouard
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, United States of America; Chemistry Graduate Program, The Ohio State University, Columbus, OH 43210, United States of America.
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, United States of America; Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, United States of America.
Bioorg Med Chem. 2025 Oct 1;128:118283. doi: 10.1016/j.bmc.2025.118283. Epub 2025 Jun 13.
Cyclic peptides have emerged as highly versatile compounds in drug development and bioengineering, offering unique structural stability, binding specificity, and reduced susceptibility to proteolysis compared to their linear counterparts. These properties make cyclic peptides valuable in a range of therapeutic applications, from antimicrobial and anticancer agents to affinity tags in protein engineering. This review provides a comprehensive overview of cyclic peptide types, synthesis methods, and the latest advances in cyclic peptide-based therapeutics. Particular emphasis has been placed on "tag-like" cyclic peptides, which can function as affinity tags for enhancing the bioactivity and targeting capabilities of larger proteins. We explore various cyclization techniques, including disulfide bridging, metal-mediated linkers, and organic reagents, that facilitate the production of both monocyclic and bicyclic peptides with optimized pharmacokinetic and stability profiles. Recent advancements in display technologies, such as phage and mRNA display, further underscore the therapeutic potential of cyclic peptides, enabling rapid identification of candidates with high affinity and selectivity for a range of targets. This review discusses the potential of cyclic peptides as affinity tags that can be engineered onto proteins of interest, bridging the gap between small molecules and larger biologics, and explores future directions for their use in enhancing protein purification, detection, and interaction studies in protein engineering projects.
环肽已成为药物开发和生物工程中用途极为广泛的化合物，与线性肽相比，具有独特的结构稳定性、结合特异性以及更低的蛋白水解敏感性。这些特性使环肽在一系列治疗应用中具有价值，从抗菌和抗癌药物到蛋白质工程中的亲和标签。本文综述全面概述了环肽的类型、合成方法以及基于环肽的治疗方法的最新进展。特别强调了“标签样”环肽，其可作为亲和标签增强更大蛋白质的生物活性和靶向能力。我们探讨了各种环化技术，包括二硫键桥连、金属介导的连接子和有机试剂，这些技术有助于生产具有优化药代动力学和稳定性特征的单环和双环肽。展示技术（如噬菌体展示和mRNA展示）的最新进展进一步突出了环肽的治疗潜力，能够快速鉴定对一系列靶点具有高亲和力和选择性的候选物。本文综述讨论了环肽作为可设计到目标蛋白质上的亲和标签的潜力，弥合小分子与更大生物制品之间的差距，并探讨了其在蛋白质工程项目中增强蛋白质纯化、检测和相互作用研究方面的未来应用方向。
