Rates of Platination of AG and GA containing double-stranded oliqonucleotides:effect of chloride concentration.

Abstract

The kinetics of the reactions between 15N-labelled cisplatin and 14-base pair duplex oligonucleotides with either 5'-AG-3' or 5'-GA-3' groupings as the principal platination site are examined in the presence of 60-80 mM chloride by [1H,15N] HSQC 2D NMR spectroscopy. The presence of chloride at these concentrations results in a five-fold decrease in the rate of hydrolysis of cisplatin to cis-[PtCl(NH3)2(OH2)]+ and a two- to twenty-fold decrease in the rate of monofunctional adduct formation. The effects on the rate of closure from monofunctional to bifunctional adducts are less well established but some of these rates appear not to be significantly reduced by the presence of added chloride. The results provide a caution that the use of chloride to quench platination reactions may not be fully effective.