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.
Showing the most recent 10 out of 24 publications
