Falconer Margaret, Smith Fiona, Surah-Narwal Sandha, Congrave Gill, Liu Zhen, Hayter Paul, Ciaramella Giuseppe, Keighley Wilma, Haddock Peter, Waldron Gareth, Sewing Andreas
Lead Discovery Technologies, Pfizer Global Research and Development, Sandwich, United Kingdom.
J Biomol Screen. 2002 Oct;7(5):460-5. doi: 10.1177/108705702237678.
Ion channels present a group of targets for major clinical indications, which have been difficult to address due to the lack of suitable rapid but biologically significant methodologies. To address the need for increased throughput in primary screening, the authors have set up a Beckman/Sagian core system to fully automate functional fluorescence-based assays that measure ion channel function. They apply voltage-sensitive fluorescent probes, and the activity of channels is monitored using Aurora's Voltage/Ion Probe Reader (VIPR). The system provides a platform for fully automated high-throughput screening as well as pharmacological characterization of ion channel modulators. The application of voltage-sensitive fluorescence dyes coupled with fluorescence resonance energy transfer is the basis of robust assays, which can be adapted to the study of a variety of ion channels to screen for both inhibitors and activators of voltage-gated and other ion channels.
离子通道是主要临床适应症的一组靶点，由于缺乏合适的快速且具有生物学意义的方法，这些靶点一直难以攻克。为满足初筛中提高通量的需求，作者建立了一个贝克曼/萨吉安核心系统，以实现基于功能荧光的检测的完全自动化，这些检测用于测量离子通道功能。他们应用电压敏感荧光探针，并使用奥罗拉公司的电压/离子探针读数器（VIPR）监测通道的活性。该系统为离子通道调节剂的完全自动化高通量筛选以及药理学表征提供了一个平台。结合荧光共振能量转移的电压敏感荧光染料的应用是可靠检测的基础，这些检测可适用于各种离子通道的研究，以筛选电压门控和其他离子通道的抑制剂和激活剂。
