Janssen Research & Development, 3210 Merryfield Row, San Diego, California 92121-1126, USA.
Anal Chem. 2012 Aug 7;84(15):6914-8. doi: 10.1021/ac301544u. Epub 2012 Jul 20.
In drug discovery, chemical library compounds are usually dissolved in DMSO at a certain concentration and then distributed to biologists for target screening. Quantitative (1)H NMR (qNMR) is the preferred method for the determination of the actual concentrations of compounds because the relative single proton peak areas of two chemical species represent the relative molar concentrations of the two compounds, that is, the compound of interest and a calibrant. Thus, an analyte concentration can be determined using a calibration compound at a known concentration. One particularly time-consuming step in the qNMR analysis of compound libraries is the manual integration of peaks. In this report is presented an automated method for performing this task without prior knowledge of compound structures and by using an external calibration spectrum. The script for automated integration is fast and adaptable to large-scale data sets, eliminating the need for manual integration in ~80% of the cases.
在药物发现中，化学文库化合物通常溶解在 DMSO 中达到一定浓度，然后分发给生物学家进行靶标筛选。定量 (1)H NMR (qNMR) 是测定化合物实际浓度的首选方法，因为两种化学物质的相对单质子峰面积代表了两种化合物的相对摩尔浓度，即感兴趣的化合物和校准剂。因此，可以使用已知浓度的校准化合物来确定分析物的浓度。化合物文库 qNMR 分析中特别耗时的一步是手动积分峰。本报告介绍了一种无需事先了解化合物结构且使用外部校准光谱即可执行此任务的自动化方法。自动化积分脚本速度快，适用于大规模数据集，在约 80%的情况下消除了手动积分的需要。
