Binding of the anticancer drug cis-dichlorodiammineplatinum to 3'(2')-guanosine monophosphate and nucleic acids

Abstract

The UV-absorption spectral characteristics of cis[Pt(NH3)2(GMP)2]-2 ([Pt(NH3)2 (Guanosine-3'(2')-monophosphate)2]-2) (abbreviated Pt (GMP)2) and cis-[Pt(NH3)2(Guanine)2]+2 (abbreviated Pt(Gua)2) were studied at acidic, neutral and alkaline pH values. The compound Pt(GMP)2 was formed by reacting GMP with cis-Pt(NH3)2Cl2(= cis-platinum) in H2O(pH approximately 6) at 24 degrees C for 7 days in the dark. Hydrolysis of Pt(GMP)2 with HClO4 to remove its sugar-phosphate moiety followed by paper chromatographic separation yielded Pt(Gua)2. Exposure to alkali did not cause any irreversible change in the absorption spectrum of Pt(GMP)2 indicating the lack of imidazole ring fission. Spectral changes for Pt(Gua)2 as compared to control Gua at neutral and alkaline pH values were quantitatively less than those reported for 7-methyl guanine in the literature. Electronic perturbation of the guanine ring system was thus found to be considerably less for platinum than for alkylation of the N7 site. These subtle differences between the platination and alkylation of Gua are of interest in view of the apparent similarities between the biological effects of cis-platinum and bifunctional alkylating agents reported in the literature.