Platinated-DNA Adducts

Table 5.3 Cisplatin half-lives (/i for reaction with duplexes having specific binding sites and percentage of total platinated DNA adducts"...

Comparison of CD spectra and 31P NMR spectra of both platinated DNA from several sources and the platinated ds decanucleotide, strongly suggets similar distortions in both cases. Molecular dynamics calculations by Kozelka et al. (64c), based on the above-mentioned decanucleotide, indicated that this kinklike structure can indeed exist. Just as in the crystals of the cts-Pt adduct of d(pGpG), an NH3—OPO3 hydrogen bond appears to be present in the calculated ds decanucleotide structure. 

The formation of intrastrand crosslinks on GG and AG base sequences in DNA could be deduced from the presence of the adducts ds-Pt(NH3)2(d(pGG)) and cis-Pt(NH3)2(d(pAG)) in digests of platinated DNA. However, no indications for the presence of GA adducts could be found, and therefore crosslinks with a GA sequence are unlikely. 

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