Rates of platination of -AG- and -GA- containing double-stranded oligonucleotides: effect of chloride concentration

The kinetics of the reactions between N-15-labelled cisplatin and 14-base p air duplex oligonucleotides with either 5'-AG-3' or 5'-GA-3' groupings as t he principal platination site are examined in the presence of 60-80 mM chlo ride by [H-1,N-15] HSQC 2D NMR spectroscopy. The presence of chloride at th ese concentrations results in a five-fold decrease in the rate of hydrolysi s of cisplatin to cis-[PtCl(NH3)(2)(OH2)](+) and a two- to twenty-fold decr ease in the rate of monofunctional adduct formation. The effects on the rat e of closure from monofunctional to bifunctional adducts are less well esta blished but some of these rates appear not to be significantly reduced by t he presence of added chloride. The results provide a caution that the use o f chloride to quench platination reactions may not be fully effective. (C) 2000 Elsevier Science Inc. All rights reserved.