THE RELEVANCE OF HYDROGEN-BONDING IN THE MECHANISM OF ACTION OF PLATINUM ANTITUMOR COMPOUNDS

被引:319
作者
REEDIJK, J
机构
[1] Department of Chemistry, Gorlaeus Laboratories, Leiden University, 2300 RA Leiden
关键词
D O I
10.1016/S0020-1693(00)92433-2
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
A brief review is presented dealing with the mechanism of action of platinum antitumor drugs with the general formula cis-PtX2(NHR2)2, in which R can be almost any organic fragment, and X can be any leaving group, such as chloride, sulfate, or (chelating bis)carboxylate. Special emphasis is given on the role of hydrogen bonding in the several reactions taking place. It turns out that the N-H group in the amine is important in determining the overall activity of the Pt compound. It is also likely to be responsible for the preferred ionic/dipolar interaction with nucleic acids, over proteins. Studies with single-stranded and double-stranded oligonucleotides have shown that the N-H group also plays a role in discriminating between adenine and guanine. Finally the stabilization of the distorted DNA, after Pt binding, has been shown to originate from N-H... O-phosphate interactions.
引用
收藏
页码:873 / 881
页数:9
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