Suppr超能文献

全球激酶筛选。前沿亲和色谱-质谱联用技术在药物发现中的应用。

Global kinase screening. Applications of frontal affinity chromatography coupled to mass spectrometry in drug discovery.

作者信息

Slon-Usakiewicz Jacek J, Dai Jin-Rui, Ng William, Foster J Estelle, Deretey Eugen, Toledo-Sherman Leticia, Redden Peter R, Pasternak Andrew, Reid Neil

机构信息

Lead Discovery and Optimization Division, Protana Inc., 251 Attwell Drive, Toronto, Ontario, M9W 7H4 Canada.

出版信息

Anal Chem. 2005 Mar 1;77(5):1268-74. doi: 10.1021/ac048716q.

Abstract

Utilizing frontal affinity chromatography with mass spectrometry detection (FAC-MS), we have identified novel applications in the discovery of small-molecule hits to protein targets that are difficult if not impossible to accomplish using traditional assays. We demonstrate for the first time an ability to distinguish between competitive ligands for the ATP and substrate sites of protein kinase C independently in the same experiment and show that ATP competitive ligands using a functionally inactive receptor tyrosine kinase can be identified. This ability of FAC-MS to simultaneously monitor binding at the ATP and substrate binding sites, as well as measure ligand binding to both active and inactive kinases, suggests that FAC-MS can be used as a "global kinase binding assay".

摘要

利用具有质谱检测功能的前沿亲和色谱法(FAC-MS),我们在发现针对蛋白质靶点的小分子命中物方面确定了新的应用,而这些应用使用传统检测方法即便不是不可能完成,也是很难实现的。我们首次证明了在同一实验中能够独立区分蛋白激酶C的ATP位点和底物位点的竞争性配体,并表明使用功能失活的受体酪氨酸激酶可以鉴定出ATP竞争性配体。FAC-MS能够同时监测ATP和底物结合位点的结合情况,以及测量配体与活性和失活激酶的结合,这表明FAC-MS可用作“全局激酶结合测定法”。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验