Platinum Binding to d(GpG) Target Sequences and Phosphorothioate Linkages in DNA Occurs More Rapidly with Increasing Oligonucleotide Length

[1H, 15N] NMR Studies of the Platination of Phosphorothioate Nucleotides − Monofunctional Sulfur Adducts versus Macrochelation

“…The large, low-frequency shift of the phosphorothioate 31 P resonance (δ ϭ Ϫ13.8) can be attributed to the direct coordination of PϭS to Pt, as observed previously. [13,14] Any 195 Pt satellites appeared to be broadened beyond detection (by chemical shift anisotropy). The 31 P NMR chemical shifts of the resonances for the phosphate 31 P atoms of Is were little affected by the binding of Pt to the oligonucleotide.…”

Determination by Electrospray Mass Spectrometry of the Outersphere Association Constants of DNA/Platinum Complexes Using 20-mer Oligonucleotides and ([Pt(NH3)4]2+, 2Cl−) or ([Pt(py)4]2+, 2Cl−)

“…The association between oligonucleotides and platinum complexes result mainly from electrostatic interactions and hydrogen bonds (14,15). Therefore, these interactions existing in solution will be maintained in the gas phase and ESMS spectra will reflect the distribution of the various species in solution, since they have strong gas phase stabilities.…”

“…It is supposed that prior to the binding of cisplatin to one or two guanines (10 -13), the aforementioned cationic complexes associate with polyanionic DNA through electrostatic interactions. Lippard and co-worker (14,15) have shown that the rate of platination increases with the length of single-stranded oligonucleotides from 8-to 16-mer, whereas single-stranded and duplex oligonucleotides of the same length displayed identical reactivity. According to these results, the authors proposed a two-step mechanism for DNA platination.…”

Synthesis and DNA Interaction of Platinum Complex/Peptide Chimera as Potential Drug Candidates

“…Typically, a cationic metal complex or metabolite is used for electrostatic interaction with the polyanionic DNA backbone. [4,[15][16][17] Association of such complexes to the DNA backbone facilitates covalent binding [18][19][20][21][22] and can thus be expected to improve the therapeutic efficacy. The lower pH and chloride concentration inside the cell compared to the blood stream allow for preferential hydrolysis of cisplatin complexes in the cellular environment, providing formation of positively charged species close to its cellular target.…”