Identification of chemically selective displacers using parallel batch screening experiments and quantitative structure efficacy relationship models.
Identification of chemically selective displacers using parallel batch screening experiments and quantitative structure efficacy relationship models.
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DOI：
10.1021/ac0341564
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发表时间：
2003-09
影响因子：
7.4
通讯作者：
N. Tugcu;Asif Ladiwala;C. Breneman;S. Cramer
中科院分区：
文献类型：
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作者：
N. Tugcu;Asif Ladiwala;C. Breneman;S. Cramer
进行平行批量筛选实验，以检查置换剂化学和盐抗衡离子如何影响阴离子交换色谱系统中批量蛋白质置换的选择性。结果表明，盐类型和置换剂化学性质均可对置换的蛋白质量产生显着影响。重要的是，结果表明，通过改变置换剂、盐抗衡离子或两者，可以诱导两种模型蛋白的相对置换的显着选择性变化。这表明通过适当选择置换剂化学和盐抗衡离子，可以在离子交换系统中开发高选择性分离。实验批量筛选数据还与各种分子描述符结合使用，基于支持向量机特征选择和回归工具生成定量结构功效关系（QSER）模型。这些模型对外部置换器测试集产生了良好的相关性和成功的预测。星图方法被证明是帮助解释 QSER 模型的强大工具。这些结果表明，该建模方法可用于置换器功效的先验预测，以及提供对置换器设计的深入了解以及为高选择性分离选择适当的流动相条件。
Parallel batch screening experiments were carried out to examine how displacer chemistry and salt counterions affect the selectivity of batch protein displacements in anion exchange chromatographic systems. The results indicate that both salt type and displacer chemistry can have a significant impact on the amount of protein displaced. Importantly, the results indicate that, by changing the displacer, salt counterion, or both, one can induce significant selectivity changes in the relative displacement of two model proteins. This indicates that highly selective separations can be developed in ion exchange systems by the appropriate selection of displacer chemistry and salt counterion. The experimental batch screening data were also used in conjunction with various molecular descriptors to generate quantitative structure efficacy relationship (QSER) models based on a support vector machine feature selection and regression tool. The models resulted in good correlations and successful predictions for an external test set of displacers. A star plot approach was shown to be a powerful tool to aid in the interpretation of the QSER models. These results indicate that this modeling approach can be employed for the a priori prediction of displacer efficacy as well as for providing insight into displacer design and the selection of proper mobile-phase conditions for highly selective separations.