Binding of Pt-antitumor Drugs to DNA

The specific interaction of these platinum compounds with cellular compo- 

Special attention is currently being given to the synthesis of new Pt com- 

In the DNA adducts of cisplatin the sites with AG and GG (A=adenosyl, G=guanosyl), are most frequently chelated, and the two bases are coordinated through N7 to cis-Pt in a head-to-head orientation. The conformational characteristics hardly change upon platination in fact only the deoxyribose moiety of the 5 -guanine has adopted an almost pure N-type conformation, compared to the S-type conformation in free d(GpG). 

Chemical shift and coupling constant analysis from the NMR spectra followed by conformational analysis suggests a rather small but significant distortion of the double helix of the larger oligonucleotides upon platination, which has been described as a kink of about 40-70 ° in the helical axis at or around the GG lesion. A structure of such a distortion Ms presented in Fig. 4.6. 

Comparison of CD spectra and NMR spectra of both platinated DNA from several sources and the platinated double-stranded (ds) decanucleotide strongly suggests similar distortions for both DNA, plasmids and oligonucleotides. 

---