A universal homogeneous assay for high-throughput determination of binding kinetics

被引：47

作者：

Schiele, Felix ^{[1
]}

Ayaz, Pelin ^{[2
]}

Fernandez-Montalvan, Amaury ^{[1
]}

机构：

[1] Bayer HealthCare, Dept Lead Discovery Berlin, Assay Dev High Throughput Screening, D-13353 Berlin, Germany

[2] Bayer HealthCare, Dept Lead Discovery Berlin, Prot Technol, Global Drug Discovery, D-13353 Berlin, Germany

来源：

ANALYTICAL BIOCHEMISTRY | 2015年 / 468卷

关键词：

Binding kinetics; High throughput; Probe competition; TR-FRET; TARGET RESIDENCE TIME; TUMOR-GROWTH INHIBITOR; LIGAND-BINDING; ZK; 304709; BIOCHEMICAL-MECHANISMS; BROMODOMAIN INHIBITORS; DOSE-ESCALATION; PHARMACOKINETICS; RECEPTORS; TOLERABILITY;

D O I：

10.1016/j.ab.2014.09.007

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

There is an increasing demand for assay technologies that enable accurate, cost-effective, and high-throughput measurements of drug-target association and dissociation rates. Here we introduce a universal homogeneous kinetic probe competition assay (kPCA) that meets these requirements. The time-resolved fluorescence energy transfer (TR-FRET) procedure combines the versatility of radioligand binding assays with the advantages of homogeneous nonradioactive techniques while approaching the time resolution of surface plasmon resonance (SPR) and related biosensors. We show application of kPCA for three important target classes: enzymes, protein-protein interactions, and G protein-coupled receptors (GPCRs). This method is capable of supporting early stages of drug discovery with large amounts of kinetic information. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：42 / 49

页数：8

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