Hoffer Laurent, Roche Philippe, Morelli Xavier
Centre de Recherche en Cancérologie de Marseille (CRCM), Aix-Marseille Université, Inserm, CNRS and Institut Paoli-Calmettes, Marseille, France.
Methods Mol Biol. 2021;2256:277-289. doi: 10.1007/978-1-0716-1166-1_16.
PDZ domains, which belong to protein-protein interaction networks, are critical for regulating important biological processes such as scaffolding, trafficking, and signaling cascades. Interfering with PDZ-mediated interactions could affect these numerous biological processes. Thus, PDZ domains have emerged as promising targets to decipher biological phenomena and potentially treat cancer and neurological diseases. In this minireview, we focus on the discovery and design of small molecule inhibitors to modulate PDZ domains. These compounds interfere with endogenous protein partners from the PDZ domain by binding at the protein-protein interface. While peptides or peptidomimetic ligands were described to modulate PDZ domains, the focus of this review is on small organic compounds.
PDZ结构域属于蛋白质-蛋白质相互作用网络，对于调节重要的生物学过程（如支架构建、运输和信号级联反应）至关重要。干扰PDZ介导的相互作用可能会影响这些众多的生物学过程。因此，PDZ结构域已成为解读生物学现象以及潜在治疗癌症和神经疾病的有前景的靶点。在这篇小型综述中，我们聚焦于调节PDZ结构域的小分子抑制剂的发现与设计。这些化合物通过在蛋白质-蛋白质界面结合来干扰来自PDZ结构域的内源性蛋白质伴侣。虽然已有报道称肽或拟肽配体可调节PDZ结构域，但本综述的重点是小有机化合物。
