Conformational changes in a single- and double-stranded nonanucleotide upon complexation of a monofunctional platinum compound as studied by 1H NMR, 31P NMR, and CD methods

The structure of the nonanucleotide d(T-C-T-C-G-T-C-T-C), after binding of a monofunctional platinum compound [PtCl(NH3)3]Cl to the N7 of the central guanine residue, is described. The observed conformational changes are limited to the central residues; the intramolecular interactions between dC(4) and dG(5) are reduced, and the sugar conformation of the platinated guanosine, dG(5), is changed from the S-type conformer toward an N-type conformer upon platination. When the complementary strand d(G-A-G-A-C-G-A-G-A) is added to the platinated nonanucleotide, a duplex is formed. The imino proton of the platinated G x C base pair is clearly observed in the 1H NMR spectrum at low temperatures. The melting temperature of the double-stranded nonanucleotide is reduced by 15-20 degree C as a result of monofunctional platinum binding to dG(5). The conformation of this Pt(NH3)3-DNA adduct is compared with the structure of a DNA fragment to which the antitumor agent cis-PtCl2(NH3)2 is bound bifunctionally. The kinked structure, which is proposed for cis-Pt(NH3)2-DNA, does not occur in the monofunctional-platinated nonanucleotide, although the double-helical structure as such is destabilized. 57 refs., 8 figs.m 2 tabs