QSAR STUDIES BY LIPOSOME ELECTROKINETIC CHROMATOGRAPHY

该项目的主要目标是研究 胶束电动毛细管色谱（MECC）与胶束 液相色谱法（MLC）用于通过 定量保留-活性关系（QRAR）和定量 分子的亲脂性。发展定量 化学结构特性与生物学特性之间的关系 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了解共同的基本 影响MECC和MLC中保留的分子相互作用， 生物活性，分配到生物膜中，或结合到 proteins.这些目标将通过以下平行研究来实现： 将MECC / MLC保留、辛醇-水分配系数 蛋白质结合和脂质体分配到溶剂化显色 用线性溶剂化能关系确定溶质参数 （LSER）。为了！充分探讨这些问题的多层面性质， 问题，我们将调查的有用性的因素为基础， 多变量分析化学计量技术，如主成分 回归和偏最小二乘法。 这项研究应导致发展独特的方法， 生物分子的物理化学性质的表征。的 由于胶束聚集体的两亲性， 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， 不同类型的相互作用的结合，以及计算 多变量分析技术处理大集合的能力 数据在多维空间中的应用将提供令人兴奋的机会 结构-活动模型。 另一个主要目标是探索这两个巨大的能力 胶束介导技术解决复杂的生物分离问题。 我们将利用定量模型的预测能力 我们的实验室已经开发出来，并将扩大 为了更好地理解移徙问题， MECC和MLC中各种生物小分子的行为。这将 包括对色谱参数的系统研究， 影响生物分析中一般感兴趣溶质的分离， 特别是药学上重要的化合物和小肽。我们 将研究计算机辅助建模的有用性， 模拟在开发快速有效的优化方法， 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.