Interaction of cisplatin and DNA-targeted 9-aminoacridine platinum complexes with DNA

Interaction of acridine- and 9-aminoacridinecarboxamide platinum complexes with DNA was investigated with respect to their DNA sequence specificity an d kinetics of binding. The DNA sequence specificity of the compounds was qu antitatively analyzed using a polymerase stop assay with the plasmid pUC19. The 9-aminoacridinecarboxamide platinum complexes exhibited a different se quence specificity to that of cisplatin, shifted away from runs of consecut ive guanines (the main binding site for cisplatin). This alteration was dep endent on chain length. Shorter chain length compounds (n = 2, 3) showed a greater difference in sequence specificity, while longer chain length compo unds (n = 4, 5) more closely resembled cisplatin. An acridinecarboxamide pl atinum complex showed a similar sequence specificity to cisplatin, revealin g that the major change of sequence specificity was due to the presence of the 9-amino substituent. A linear amplification system was used to investig ate the time course of the reaction. The presence of an intercalating group (acridinecarboxamide or 9-aminoacridinecarboxamide) greatly increased the rate of reaction with DNA; this is proposed to be due to a different reacti on mechanism with DNA (direct displacement by the N-7 of guanine).