Automatic Analysis of Quantitative NMR Data of Pharmaceutical Compound Libraries
Automatic Analysis of Quantitative NMR Data of Pharmaceutical Compound Libraries
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DOI：
10.1021/ac301544u
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发表时间：
2012-08-07
影响因子：
7.4
通讯作者：
Leo, Gregory C.
中科院分区：
文献类型：
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作者：
Liu, Xuejun;Kolpak, Michael X.;Leo, Gregory C.
在药物发现中，化学库化合物通常以一定浓度溶解在DMSO中，然后分发给生物学家进行靶点筛选。定量H-1 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个质子峰面积代表两种化合物（即目标化合物和校准品）的相对摩尔浓度。因此，可以使用已知浓度的校准化合物来确定分析物浓度。化合物库的qNMR分析中的一个特别耗时的步骤是峰的手动积分。在本报告中，提出了一种自动化的方法，用于执行这项任务，而无需事先了解化合物的结构，并通过使用外部校准光谱。用于自动集成的脚本速度快，适用于大规模数据集，在80%的情况下无需手动集成。
In drug discovery, chemical library compounds are usually dissolved in DMSO at a certain concentration and then distributed to biologists for target screening. Quantitative H-1 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 similar to 80% of the cases.