title: The sequence selectivity of DNA-targeted 9-aminoacridine cisplatin analogues in a telomere-containing DNA sequence.
abstract: In this study, the detailed DNA sequence specificity of four acridine Pt complexes was examined and compared with that of cisplatin. The DNA sequence specificity was determined in a telomere-containing DNA sequence using a polymerase stop assay, with a fluorescent primer and an automated capillary DNA sequencer. The Pt compounds included an acridine intercalating moiety that was modified to give a 9-aminoacridine derivative, a 7-methoxy-9-aminoacridine derivative, a 7-fluoro-9-aminoacridine derivative and a 9-ethanolamine-acridine derivative. Compared with cisplatin, the DNA sequence specificity was most altered for the 7-methoxy-9-aminoacridine compound, followed by the 9-aminoacridine derivative, the 7-fluoro-9-aminoacridine compound and the 9-ethanolamine-acridine derivative. The DNA sequence selectivity for the four acridine Pt complexes was shifted away from runs of consecutive guanines towards single guanine bases, especially 5'-GA dinucleotides and sequences that contained 5'-CG. The sequence specificity was examined in telomeric and non-telomeric DNA sequences. Although it was found that telomeric DNA sequences were extensively damaged by the four acridine Pt complexes, there was no extra preference for telomeric sequences.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Moumita
authors.initials: M
authors.lastname: Paul
authors.forename: Vincent
authors.initials: V
authors.lastname: Murray
mesh_terms: D000585:Aminacrine / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001483:Base Sequence; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D016615:Telomere / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007364:Intercalating Agents; D000585:Aminacrine; D004247:DNA; D002945:Cisplatin