QSAR STUDIES BY LIPOSOME ELECTROKINETIC CHROMATOGRAPHY

该项目的一个主要目标是调查 胶束电动毛细管色谱与胶束 高效液相色谱(MLC)用于生物活性的预测 定量保留-活性关系(QRAR)和定量 具有分子的亲脂性。数量化的发展 化学结构性质与生物学的关系 活动在药物设计领域产生了巨大的影响， 毒理学和环境监测。 我们的目标是更好地理解 影响MECC和MLC保留率的分子相互作用及其原因 生物活性，分割成生物膜，或结合到 蛋白质。这些目标将通过并行研究实现 MECC/MLC保留率、辛醇-水分配系数、 蛋白质结合和脂质体对溶致变色剂的分配 用线性溶剂化能关系确定溶质参数 (Lser)。为了!充分探索这些问题的多维本质 问题，我们将调查基于因素的、 主成分等多元分析化学计量学技术 QRAR建模中的回归和偏最小二乘。 这项研究应该导致开发独特的方法来 生物分子的物理化学性质的表征。这个 胶束聚集体的两亲性与仿生结合 和有组织的性质，MECC和MLC技术的巨大能力 在物理化学分析中，它们的灵活性和通用性 不同类型的交互作用的结合，以及计算 多变量分析技术在大样本处理中的作用 多维空间中的数据应该会提供令人兴奋的机会 在结构-活动模型中。 另一个主要目标是探索这两者的巨大能力 胶束介导的解决复杂生物分离问题的技术。 我们将利用量化模型的预测能力 已经在我们的实验室开发，并将扩大范围 这些模型是为了更好地理解迁徙 多种生物小分子在MECC和MLC中的行为。这将是 包括对色谱参数的系统研究，这些参数 影响生物分析中普遍感兴趣的溶质的分离， 具体地说，是药用上重要的化合物和小肽。我们 将研究计算机辅助建模的用处， 仿真在开发快速有效的优化方法中的应用 MECC和MLC分离。

A primary goal of this project is to investigate the usefulness of Micellar Electrokinetic Capillary Chromatography (MECC) and Micellar Liquid Chromatography (MLC) for prediction of bioactivity through Quantitative Retention -Activity Relationships (QRAR) and for quantitation of lipophilic character of molecules. The development of quantitative relationships between chemical structural properties and biological activity has had a tremendous impact in the fields of drug design, toxicology, and environmental monitoring. Our aim is to achieve a better understanding of the common underlying molecular interactions that influence retention in MECC and MLC and cause biological activity, partitioning into biomembranes, or binding to proteins. These goals will be realized through parallel studies of correlating MECC / MLC retention, octanol-water partition coefficient, proteins binding, and liposomes partitioning to the Solvatochromic Parameters of solutes through Linear Solvation Energy Relationships (LSER). In order to! fully explore the multidimensional nature of these problems, we will investigate the usefulness of the factor - based, multivariate analysis chemometric techniques such as principal component regression and partial least square in QRAR modeling. This research should lead to the development of unique methodologies for characterization of physicochemical properties of biomolecules. The combination of biomimicry of micellar aggregates due to their amphiphilic and organized nature, the enormous capabilities of MECC and MLC techniques in physicochemical analysis, their flexibility and versatility for incorporation of different types of interactions, and the computional power of the mutivariate analysis techniques for treatment of a large set of data in a multidimensional space should provide exciting opportunities in structure - activity modeling. Another major goal is to explore the enormous capabilities of these two micellar mediated techniques for solving complex bioseparation problems. We will take advantage of the predictive power of the quantitatve models that have been developed in our laboratory, and will extend the range of these models in order to achieve a better understanding of migration behavior of a variety of small biomolecules in MECC and MLC. This will include systematic studies of the chromatographic parameters that influence separation of solutes of general interest in bioanalysis, specifically pharmaceutically important compounds and small peptides. We will investigate the usefulness of computer assisted modeling and, simulation in developing rapid and effective methods for optimization of MECC and MLC separations.