ELECTROSTATICS RATHER THAN CONFORMATION CONTROL THE OXIDATION OF DNA BY THE ANIONIC REAGENT PERMANGANATE

Kinetic study was used to compare permanganate oxidation of oligonucleotides and evaluate the structural basis for its specificity of reaction. The rate of oligonucleotide consumption was consistently dominated by reaction of unpaired and solvent accessible thymine residues, the primary targets of modification. Formation of fully complementary duplex structures suppressed reaction of the single-stranded oligonucleotides by as much as 20-fold and revealed a basal rate of modification that no longer correlated to the presence of thymine. Insertion of a mispaired or unpaired thymine into a duplex structure modestly enhanced the overall degradation rate of DNA. While steric effects should not be discounted, electrostatic effects appeared to be the major determinant in permanganate selectivity. The oxidation rate of thymidine 5'-monophosphate and thymine residues in a single-stranded oligonucleotide approached the rate of thymidine only when high salt concentration was present to shield the repulsion of the anionic reactants. Oxidation of duplex structures was also activated by 10- to 25-fold when the sodium chloride concentration was increased from 0.1 to 4.0 M.