The DNA sequence selectivity of maltolato-containing cisplatin analogues in purified plasmid DNA and in intact human cells.
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 IC(50) 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.
Cairns
Murray J
MJ
University of New South Wales, Sydney, Australia.
Carland
Michael
M
McFadyen
W David
WD
Denny
William A
WA
Murray
Vincent
V
D001483:Base Sequence; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D009942:Organometallic Compounds; D010957:Plasmids / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification
D009942:Organometallic Compounds; D004247:DNA; D002945:Cisplatin