Tu Licheng, Wang Dongyuan, Li Zigang
State Key Laboratory of Chemical Oncogenomics, Peking University, Shenzhen Graduate School, Peking, China.
Methods Mol Biol. 2019;2001:107-131. doi: 10.1007/978-1-4939-9504-2_7.
Abnormal protein-protein interactions (PPIs) are the basis of multiple diseases, and the large and shallow PPI interfaces make the target "undruggable" for traditional small molecules. Peptides, emerging as a new therapeutic modality, can efficiently mimic PPIs with their large scaffolds. Natural peptides are flexible and usually have poor serum stability and cell permeability, features that limit their further biological applications. To satisfy the clinical application of peptide inhibitors, many strategies have been developed to constrain peptides in their bioactive conformation. In this report, we describe several classic methods used to constrain peptides into a fixed secondary structure which could significantly improve their biophysical properties.
异常的蛋白质-蛋白质相互作用（PPI）是多种疾病的基础，而PPI界面大且浅使得传统小分子难以靶向。肽作为一种新兴的治疗方式，能够通过其大的支架有效地模拟PPI。天然肽具有灵活性，但通常血清稳定性和细胞通透性较差，这些特性限制了它们的进一步生物学应用。为了满足肽抑制剂的临床应用，人们已经开发了许多策略来将肽限制在其生物活性构象中。在本报告中，我们描述了几种用于将肽限制为固定二级结构的经典方法，这些方法可以显著改善其生物物理性质。
