Hot spot-based design of small-molecule inhibitors for protein-protein interactions

被引：107

作者：

Guo, Wenxing ^{[1
]}

Wisniewski, John A. ^{[1
]}

Ji, Haitao ^{[1
]}

机构：

[1] Univ Utah, Dept Chem, Ctr Cell & Genome Sci, Salt Lake City, UT 84112 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 11期

关键词：

Protein-protein interactions; Inhibitor; Hot spots; Rational design; Selectivity; CHARACTERIZING BINDING-SITES; HIGH-AFFINITY; ACCURATE PREDICTION; ENERGY CALCULATIONS; TRANSIENT POCKETS; WATER EXCLUSION; FAMILY PROTEINS; LEAD DISCOVERY; POTENT; RESIDUES;

D O I：

10.1016/j.bmcl.2014.03.095

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Protein-protein interactions (PPIs) are important targets for the development of chemical probes and therapeutic agents. From the initial discovery of the existence of hot spots at PPI interfaces, it has been proposed that hot spots might provide the key for developing small-molecule PPI inhibitors. However, there has been no review on the ways in which the knowledge of hot spots can be used to achieve inhibitor design, nor critical examination of successful examples. This Digest discusses the characteristics of hot spots and the identification of druggable hot spot pockets. An analysis of four examples of hot spot-based design reveals the importance of this strategy in discovering potent and selective PPI inhibitors. A general procedure for hot spot-based design of PPI inhibitors is outlined. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：2546 / 2554

页数：9

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