Guanine, cisplatin compounds

Direct reactions with DNA serve as the molecular basis for the action of several anti-tumor drugs. Cancer is primarily a disease of uncontrolled cell growth, and cell growth depends on DNA synthesis. Cancer cells are often more sensitive than normal cells to compounds that damage DNA. For example, the anti-tumor drug cisplatin reacts with guanine bases in DNA and the daunomycin antibiotics act by inserting into the DNA chain between base pairs. In either case, these biochemical events can lead to the death of a tumor cell. 

Transplatin reacts 360 times faster than cisplatin with glutathione [27], a reaction likely to remove platinum from the cell, through ATP-dependent efflux [28]. It has been shown that a thioether ligand on a platinum triamine complex can be slowly replaced by a guanine-N(7), suggesting a possible platinum transporter role for such thioether compounds towards DNA [6], (This topic is discussed in the contribution by J. Reedijk and J. M. Teuben.)... 

Cisplatin (cis-dichlorodiammineplatinum cisDDP) belongs to one of the most frequently explored platinum compounds since Rosenberg s discovery of its anticancer activities.1 It was found that cisplatin makes a bridge connection between two (usually) adjacent guanine bases in DNA predominately forming 1,2-intrastrand GpG complexes (about 65% of the occurrences). Some other intrastrand coordinations occur less frequently, namely with the l,2-d(ApG) and the l,3-d(GpXpG) base sequences. However, coordination to the l,2-d(ApA) or the l,2-d(GpA) fragment was observed only very rarely. 

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