Interaction of cis-[Pt(NH3)2(H2O)2](NO3)2 with ribose and deoxyribose diguanosine phosphates

Abstract

GpG [ribose diguanosine monophosphate; 4 .times. 10-4 M], d(GpG) [deoxyribose diguanosine monophosphate; 10-5 M] and d(pGpG) [deoxyribose diguanosine diphosphate; 10-5 M] were reacted with the antitumor agent cis-[Pt(NH3)2(H2O)2](NO3)2 [cis-diammine diaquoplatinum dinitrate] (Pt/dinucleotide) in water at pH 5.5 and 37.degree. C. In each case a single product is formed. The 3 complexes were characterized by proton NMR (1H NMR) and circular dichroism (CD) analyses. They are N(7)-N(7) chelates of the metal with an anti-anti configuration of the bases. They present a conformational change on deprotonation of guanine N(1)H whose pKa is .apprx. 8.7 (D2O). Their CD spectra, compared to those of the free dinucleotides, exhibit an increase of ellipticity in the 275-nm region, which can be qualitatively related to the characteristic increase reported for plantinated DNA and poly(dG) .cntdot. poly(dC). These results are in favor of the hypothesis of intrastrand cross-linking of adjacent guanines, by the cis-PtII(NH3)2 moiety, after a local denaturation of DNA.