Abstract
The sequence specificity of the anti-tumour drug, cisplatin, was determined in a DNA sequence that contained seven telomeric repeats and a run of ten consecutive guanine bases. Cisplatin preferentially forms DNA adducts at consecutive guanine sequences. Hence these DNA sequences were examined in order to gain an insight into the important human genomic regions that are damaged by cisplatin. A polymerase stop/linear amplification assay was employed with an automated DNA capillary sequencer and laser-induced fluorescence detection to quantitatively determine the DNA sequence specificity of cisplatin in a plasmid clone containing seven telomeric repeats and a sequence of ten consecutive guanine bases. It was found that cisplatin preferentially damaged the ten consecutive guanine sequence although the telomeric DNA sequences were also a major site of cisplatin adduct formation.
Keywords: Capillary electrophoresis, Cisplatin, Consecutive guanines, Linear amplification, Polymerase stop assay, Sequence specificity, Telomeres, electropherogram, densitometry, spectroscopy
Anti-Cancer Agents in Medicinal Chemistry
Title: The Sequence Specificity of the Anti-tumour Drug, Cisplatin, in Telomeric DNA Sequences Compared with Consecutive Guanine DNA Sequences
Volume: 12 Issue: 3
Author(s): Vincent Murray and Niruba Kandasamy
Affiliation:
Keywords: Capillary electrophoresis, Cisplatin, Consecutive guanines, Linear amplification, Polymerase stop assay, Sequence specificity, Telomeres, electropherogram, densitometry, spectroscopy
Abstract: The sequence specificity of the anti-tumour drug, cisplatin, was determined in a DNA sequence that contained seven telomeric repeats and a run of ten consecutive guanine bases. Cisplatin preferentially forms DNA adducts at consecutive guanine sequences. Hence these DNA sequences were examined in order to gain an insight into the important human genomic regions that are damaged by cisplatin. A polymerase stop/linear amplification assay was employed with an automated DNA capillary sequencer and laser-induced fluorescence detection to quantitatively determine the DNA sequence specificity of cisplatin in a plasmid clone containing seven telomeric repeats and a sequence of ten consecutive guanine bases. It was found that cisplatin preferentially damaged the ten consecutive guanine sequence although the telomeric DNA sequences were also a major site of cisplatin adduct formation.
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Cite this article as:
Murray Vincent and Kandasamy Niruba, The Sequence Specificity of the Anti-tumour Drug, Cisplatin, in Telomeric DNA Sequences Compared with Consecutive Guanine DNA Sequences, Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (3) . https://dx.doi.org/10.2174/187152012800228742
DOI https://dx.doi.org/10.2174/187152012800228742 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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