Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands.
Department of Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45117 Essen, Germany.
Molecules. 2018 Jun 8;23(6):1386. doi: 10.3390/molecules23061386.
In recent years, targeting the complex network of protein⁻protein interactions (PPIs) has been identified as a promising drug-discovery approach to develop new therapeutic strategies. 14-3-3 is a family of eukaryotic conserved regulatory proteins which are of high interest as potential targets for pharmacological intervention in human diseases, such as cancer and neurodegenerative and metabolic disorders. This viewpoint is built on the “hub” nature of the 14-3-3 proteins, binding to several hundred identified partners, consequently implicating them in a multitude of different cellular mechanisms. In this review, we provide an overview of the structural and biological features of 14-3-3 and the modulation of 14-3-3 PPIs for discovering small molecular inhibitors and stabilizers of 14-3-3 PPIs.
近年来，靶向蛋白质-蛋白质相互作用（PPIs）的复杂网络已被确定为一种很有前途的药物发现方法，可用于开发新的治疗策略。14-3-3 是一组真核保守调节蛋白，作为药物干预人类疾病（如癌症以及神经退行性和代谢紊乱）的潜在靶点，受到了极大的关注。这一观点基于 14-3-3 蛋白的“枢纽”性质，它可以结合几百种已识别的伴侣，从而使它们牵涉到多种不同的细胞机制中。在这篇综述中，我们概述了 14-3-3 的结构和生物学特征，以及 14-3-3 PPI 的调节，以发现 14-3-3 PPI 的小分子抑制剂和稳定剂。
