Filling Blank Spots on the Map: Identification of Ligand Binding Modes and Interacting Water Molecules for Brd4-BD1 by WaterLOGSY Titrations,Journal of Medicinal Chemistry

当前位置： X-MOL 学术 › J. Med. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Filling Blank Spots on the Map: Identification of Ligand Binding Modes and Interacting Water Molecules for Brd4-BD1 by WaterLOGSY Titrations
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2017-10-30 00:00:00 , DOI: 10.1021/acs.jmedchem.7b01497
Ann-Christin Pöppler ₁

Affiliation

Fragment-based drug discovery and continuous improvement of existing protein inhibitors rely on the knowledge of exactly how and how strongly a range of small molecules bind to their respective protein targets. By increasing the (perdeuterated) protein concentration, WaterLOGSY titration experiments give access to ligand binding modes even in the case of weak binders as well as to the location of protein-bound water in the surroundings of the ligand. On the basis of these findings, specific chemical modifications of the ligand could be shown to yield significantly enhanced binding affinities.

中文翻译：

填补地图上的空白点：通过WaterLOGSY滴定鉴定Brd4-BD1的配体结合模式和相互作用的水分子

基于片段的药物发现和对现有蛋白抑制剂的不断改进，取决于对一系列小分子如何以及如何强烈结合其各自的蛋白靶标的了解。通过增加（氘化）蛋白质浓度，即使在弱结合剂的情况下，WaterLOGSY滴定实验也可以访问配体结合模式，还可以访问结合蛋白的水在配体周围的位置。基于这些发现，配体的特定化学修饰可以显示出明显增强的结合亲和力。

更新日期：2017-10-30

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11