CONFORMATIONAL DIFFERENCES BETWEEN THE ADDUCTS OF CIS-DDP AND TRANS-DDP WITH THE TRINUCLEOTIDE D(GPTPG) - A H-1 AND (31)NMR INVESTIGATION

The results of a binding study of cis-Pt(NH3)2Cl2 (cis-DDP) and trans-Pt(NH3)2Cl2 (trans-DDP) with the trinucleotide d(GpTpG) are described. The structure and conformation of the bis-guanine (N7) chelates formed have been determined using high-resolution NMR. The results first of all affirmed the expected complete deshielding of the intervening thymine base in both the cis and the trans adduct. The sugar rings and the backbone of both adducts show B-DNA type characteristics, except for the 5' guanosine unit and the attached phosphate of the trans-Pt(NH3)2-d(GpTpG) adduct. The first sugar ring of this latter adduct is restricted to a pure N conformation. In contrast, platination of a guanine base without formation of a chelate ring has only a minor effect on the conformational equilibrium of the sugar ring. The P-31 NMR chemical shifts of the trans-Pt(NH3)2-chelate and their temperature-dependent behavior suggest that the restraint of the conformation of the sugar ring is accompanied by a change in the torsion angles of the phosphate group attached to this sugar ring compared to B-DNA. The changes in the backbone probably originate from the formation of a strained chelate ring and might play a role in the recognition of this adduct by repair enzymes.