Direct Molecular Interaction of Phenylalanine with DNA Measured by Reversed-Phase HPLC

At present, great interest exists in relatively small molecular weight compounds that can interact with DNA in a site-specific manner. A rapid and successful way of monitoring such interactions was achieved by reversed-phase HPLC based on DNA peak size exclusion (1).Phenylalanine (Phe), a biogenic small molecule and an essential amino acid in humans, has been a diagnostic tool for detecting phenylketonouria, a metabolic inherited disease. On the basis of the charge and shape of Phe, we tried to measure in vitro the possible interaction of Phe with DNA by using calf thymus DNA. We also attempted a preliminary approach regarding a Phe mechanism of action on DNA by using compounds structurally related to the known antitumor antibiotic doxorubicin.DNA binding was evaluated according to the method of Karikas et al. (1). Calf thymus DNA was purchased from Sigma Chemical Co., and doxorubicin was from Pharmacia. HPLC-grade solvents were obtained from Lab Scan. A Hewlett-Packard …