Protein-Protein Interactions as New Targets for Ion Channel Drug Discovery.
Protein-Protein Interactions as New Targets for Ion Channel Drug Discovery.
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发表时间：
2013-12
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通讯作者：
Svetla Stoilova-McPhie;Syed R Ali;F. Laezza
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作者：
Svetla Stoilova-McPhie;Syed R Ali;F. Laezza
蛋白质-蛋白质相互作用（PPI）是提供几乎所有细胞过程中的信号传导基础的关键分子元件。这些分子相互作用的精确性和特异性激发了人们对PPI表面作为药物发现新靶点的强烈兴趣，特别是针对中枢神经系统（CNS）中的离子通道，其中选择性和特异性对于开发具有有限副作用的药物至关重要。离子通道是由多个调节蛋白组装而成的大跨膜结构域蛋白，这些调节蛋白结合到通道的细胞内部分。这些大分子复合物难以分离、纯化和重组，这对靶向这些PPI用于药物发现目的构成了重大障碍。在这里，我们将提供PPI的显着特点的简短概述，并讨论成功的研究集中在蛋白质通道的相互作用，可以激发新的药物发现运动针对离子通道复合物。
Protein-protein interactions (PPI) are key molecular elements that provide the basis of signaling in virtually all cellular processes. The precision and specificity of these molecular interactions have ignited a strong interest in pursuing PPI surfaces as new targets for drug discovery, especially against ion channels in the central nervous system (CNS) where selectivity and specificity are vital for developing drugs with limited side effects. Ion channels are large transmembrane domain proteins assembled with multiple regulatory proteins binding to the intracellular portion of channels. These macromolecular complexes are difficult to isolate, purify and reconstitute, posing a significant barrier in targeting these PPI for drug discovery purposes. Here, we will provide a short overview of salient features of PPI and discuss successful studies focusing on protein-channel interactions that could inspire new drug discovery campaigns targeting ion channel complexes.