The sequence selectivity of DNA-targeted 9-aminoacridine cisplatin analogues in a telomere-containing DNA sequence |
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Authors: | Moumita Paul Vincent Murray |
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Institution: | (1) School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, 2052, Australia; |
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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. |
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