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靶向蛋白质-蛋白质相互作用以进行药物研发。

Targeting protein-protein interactions for drug discovery.

作者信息

Fry David C

机构信息

Roche Research Center, 340 Kingsland Street, Nutley, NJ, 07110, USA,

出版信息

Methods Mol Biol. 2015;1278:93-106. doi: 10.1007/978-1-4939-2425-7_6.

Abstract

Protein-protein interactions are associated with key activities and pathways in the cell, and in that regard are promising targets for drug discovery. However, in terms of small molecule drugs, this promise has not been realized. The physical nature of many protein-protein interaction surfaces renders them unable to support binding of small drug-like molecules. In addition, there are other unique hurdles presented by this class that make the drug development process difficult and risky. Nevertheless, success stories have begun to steadily appear in this field. These experiences are starting to provide general strategies and tools to help overcome the problems inherent in pursuing protein-protein interaction targets. These lessons should improve the rate of success as these systems are pursued in the future.

摘要

蛋白质-蛋白质相互作用与细胞中的关键活动和途径相关,因此是药物研发的有前景的靶点。然而,就小分子药物而言,这一前景尚未实现。许多蛋白质-蛋白质相互作用表面的物理性质使其无法支持类药物小分子的结合。此外,这类相互作用还存在其他独特的障碍,使得药物开发过程困难且有风险。尽管如此,该领域已开始不断出现成功案例。这些经验开始提供通用的策略和工具,以帮助克服在追求蛋白质-蛋白质相互作用靶点时所固有的问题。随着未来对这些系统的深入研究,这些经验教训应能提高成功率。

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