Protein–protein interactions (PPI) are involved in all cellular processes and many represent attractive therapeutic targets. However, the frequently rather flat and large interaction areas render the identification of small molecular PPI inhibitors very challenging. As an alternative, peptide interaction motifs derived from a PPI interface can serve as starting points for the development of inhibitors. However, certain proteins remain challenging targets when applying inhibitors with a competitive mode of action. For that reason, peptide-based ligands with an irreversible binding mode have gained attention in recent years. This review summarizes examples of covalent inhibitors that employ peptidic binders and have been tested in a biological context.

中文翻译：

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基于肽的蛋白质-蛋白质相互作用共价抑制剂

蛋白质-蛋白质相互作用 (PPI) 参与所有细胞过程，许多代表有吸引力的治疗靶点。然而，经常相当平坦和大的相互作用区域使得小分子 PPI 抑制剂的鉴定非常具有挑战性。作为替代方案，源自 PPI 界面的肽相互作用基序可以作为开发抑制剂的起点。然而，当应用具有竞争作用模式的抑制剂时，某些蛋白质仍然具有挑战性的目标。出于这个原因，具有不可逆结合模式的基于肽的配体近年来受到关注。本综述总结了使用肽结合剂并已在生物学背景下进行测试的共价抑制剂的示例。