Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/924985

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Title
The DNA sequence selectivity of maltolato-containing cisplatin analogues in purified plasmid DNA and in intact human cells
Author/Creator
Cairns, Murray J.;  Carland, Michael;  Mcfadyen, W. David;  Denny, William A.;  Murray, Vincent
Institution
The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
Description
Cisplatin analogues with an attached DNA binding moiety have a higher affinity for DNA, but often suffer from poor aqueous solubility. In this study we examined the DNA sequence specificity of more soluble cisplatin analogues containing the maltolato leaving group in both purified DNA and in intact human cells. In both environments the DNA sequence specificity of these analogues was very similar to cisplatin. However, in purified DNA a higher concentration of the two maltolato-containing analogues was needed to achieve a similar level of DNA damage as cisplatin. This difference in reactivity was not observed in intact cells as the two maltolato-containing complexes were capable of producing a similar level of damage as cisplatin at comparable concentrations. This was consistent with the IC50 values obtained for both cisplatin and the maltolato compounds which were also similar. This study indicated that maltolato can be utilised as the leaving group to increase the aqueous solubility of cisplatin analogues without reducing their biological activity.
Relation
Journal of Inorganic Biochemistry Vol. 103, Issue 8, p. 1151-1155
Publisher Link
http://dx.doi.org/10.1016/j.jinorgbio.2009.06.001
Date
2009
Publisher
Elsevier
Keyword(s)
diammineplatinum(II);  maltolato;  sequence selectivity;  human cells
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/924985
Identifier
ISSN:0162-0134
Reviewed
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Subject
"Journal of Inorganic Biochemistry"
 
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