Demethylation of O6-methylguanine in DNA by O6-methylguanine-DNA methyltransferase: synthesis and characterization of O6,9-dimethylguanine coordinated with cis-platin at the N7-position.
In order to investigate the chemical characteristics of O6-methylguanines, the substrate of O6-methylguanine-DNA methyltransferase, cis[PtCl(NH3)2(O6,9-dimethylguanine-7)]NO3, a 1:1 complex of cis-platin with O6,9-dimethylguanine, was synthesized and its demethylation rate, pKa, X-ray structure and cytotoxicity were determined.
Terashima
I
I
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Yamagata
Y
Y
Yamagami
N
N
Kohda
K
K
D000818:Animals; D002945:Cisplatin / Q000031:analogs & derivatives / Q000737:chemistry; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000633:toxicity; D007700:Kinetics; D007939:Leukemia L1210 / Q000188:drug therapy; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D051379:Mice; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000633:toxicity
D009944:Organoplatinum Compounds; C088123:cis-diamminechloro(O(6),9-dimethylguanine-7)platinum(II) nitrate; D006147:Guanine; D004247:DNA; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002945:Cisplatin