Cyclotides are plant-derived cyclic, disulfide-rich peptides with a unique cyclic cystine knot topology that confers them with remarkable structural stability and resistance to proteolytic degradation. Recently, cyclotides have emerged as promising scaffold molecules for designing peptide-based therapeutics. Here, we provide examples of how engineering cyclotides using molecular grafting may lead to the development of novel peptide ligands of G protein-coupled receptors (GPCRs), today's most exploited drug targets. Integrating bioactive epitopes into stable cyclotide scaffolds can lead to improved pharmacokinetics and oral activity as well as selectivity and high enzymatic stability. We also discuss and highlight the importance of engineered cyclotides as novel tools to study GPCR signaling.

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利用环肽设计和开发新型肽 GPCR 配体

环肽是植物来源的环状、富含二硫化物的肽，具有独特的环状胱氨酸结拓扑结构，赋予它们显着的结构稳定性和对蛋白水解降解的抵抗力。最近，环肽已成为用于设计基于肽的疗法的有前途的支架分子。在这里，我们提供了一些例子，说明使用分子嫁接的工程环肽如何导致 G 蛋白偶联受体 (GPCR) 的新型肽配体的开发，GPCR 是当今最受开发的药物靶标。将生物活性表位整合到稳定的环肽支架中可以改善药代动力学和口服活性以及选择性和高酶稳定性。我们还讨论并强调了工程环肽作为研究 GPCR 信号传导的新工具的重要性。