NOVEL HYDROPHOBIC INDEX FOR LFER OF ANTITUMOR AGENTS

本研究的目标是进一步开发HIGH的潜力 高效液相色谱作为物理化学研究的工具 测量以获得关于分子性质的信息 生物活性物质，如抗癌药物，因此 促进设计更有效的抗肿瘤药物。在此基础上 对线性自由能关系的保留数据进行了反转 将在广泛的条件下使用相色谱来 二元疏水指数的建立 药物的疏水性。由此得到的疏水指数将为 与已知的抗肿瘤药物生物活性相关。这个 多肽的层析保留行为将在 为了建立定量的结构保留关系 线性自由能关系的基础。预计结果将会产生 关于此类生物低聚物的分子性质的信息 它们的构象受到关注。此外，还将尝试 将所获得的疏水指数与一定的动力学参数相关联 参数。多肽和蛋白质在表面上的吸附特性 具有层析和生物学意义的将被调查和 分子结构与分子结构参数的关系 将寻求吸附等温线。由于预期的重要性， 肿瘤治疗中的大分子药物及其高效液相色谱研究进展 生物聚合物的研究范围扩大到对 疏水相互作用对蛋白质动态疏水性质的影响 具有已知表面性质的固定相的层析。它是 希望这项研究将导致制定一个疏水指数 反映其生物动力学疏水性的生物大分子。型号 已知分子结构的蛋白质覆盖了广泛的分子范围 重量和疏水性质和一组七个二氢叶酸 只有一种氨基酸不同的还原酶将被研究。

The goal of this study is to develop further the potential of high performance liquid chromatography as a tool for physico-chemical measurements in order to gain information on the molecular properties of biologically active substances such as anti-cancer drugs and thus facilitate the design of more potent antineoplastic agents. On the basis of linear free energy relationships retention data obtained in reversed phase chromatography over a wide range of conditions will be used for establishment of a binary hydrophobic index in order to characterize the hydrophobicity of drugs. The hydrophobic indices thus obtained will be correlated with known biological activity of antineoplastic drugs. The chromatographic retention behavior of peptides will be investigated in order to formulate quantitative structure retention relationships on the basis of linear free energy relationships. The result is expected to yield information on the molecular properties of such biooligomers as far as their conformation is concerned. Furthermore, an attempt will be made to correlate the hydrophobic indices thus obtained with certain kinetic parameters. The adsorption properties of peptides and proteins on surfaces having chromatographic and biological significance will be investigated and a relationship between the molecular structure and the parameters of the adsorption isotherms will be sought. Due to the expected importance of macromolecular drugs in cancer treatment and recent advances in the HPLC of biopolymers the scope of the study is expanded to the investigation of dynamic hydrophobic properties of proteins by hydrophobic interaction chromatography with stationary phases of known surface properties. It is hoped that the study will lead to formulation of a hydrophobic index for biomacromolecules that reflects their biodynamic hydrophobicity. Model proteins of known molecular structure covering a wide range of molecular weights and hydrophobic properties and a group of seven dihydrofolate reductases differing only in a single amino acid will be investigated.