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Rational drug design via intrinsically disordered protein

机译:通过内在无序的蛋白质进行合理的药物设计

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Despite substantial increases in research funding by the pharmaceutical industry, drug discovery rates seem to have reached a plateau or perhaps are even declining, suggesting the need for new strategies. Protein-protein interactions have long been thought to provide interesting drug discovery targets, but the development of small molecules that modulate such interactions has so far achieved a low success rate. In contrast to this historic trend, a few recent successes raise hopes for routinely identifying druggable protein-protein interactions. In this Opinion article, we point out the importance of coupled binding and folding for protein-protein signalling interactions generally, and from this and associated observations, we develop a new strategy for identifying protein-protein interactions that would be particularly promising targets for modulation by small molecules. This novel strategy, based on intrinsically disordered protein, has the potential to increase significantly the discovery rate for new molecule entities.
机译:尽管制药行业的研究经费大量增加,但药物发现率似乎已经达到平稳甚至下降的趋势,这表明需要采取新的策略。长期以来,人们一直认为蛋白质-蛋白质相互作用可提供有趣的药物发现靶标,但迄今为止,调节这种相互作用的小分子的开发成功率较低。与这一历史趋势相反,最近的一些成功为常规识别可药物化的蛋白质-蛋白质相互作用提供了希望。在此“意见”文章中,我们指出了结合结合和折叠对于蛋白质-蛋白质信号相互作用的总体重要性,并且从这一观点和相关观察中,我们开发了一种鉴定蛋白质-蛋白质相互作用的新策略,该策略将是特别有希望成为调节蛋白靶点的靶标。小分子。这种基于内在无序蛋白的新颖策略,有可能显着提高新分子实体的发现率。

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