Complex formation between a DNA duplex and lipid-like spermine derivatives: Hydrophobic protection of DNA from one-electron oxidation

The one-electron oxidation of DNA leads to formation of a nucleobase radical cation that can migrate to a distant site where it is trapped by H2O or O-2 to form a "damaged" guanine that is revealed as strand cleavage when the irradiated sample is treated with piperidine. We prepared a series of alkyl-substituted spermine derivatives and assessed their effect on the oxidative reactions of DNA induced by photoexcitation of a covalently linked anthraquinone derivative. The spermine compounds are polycations and bind nonselectively to DNA. When the spermine derivative is substituted with C-S alkyl chains, it shows lipid-like properties. The reaction of the radical cation at guanine is affected by this lipid-like spermine. The distance dependence of the migration process becomes weaker, and the efficiency of strand cleavage is reduced. These results are attributed to the formation of a hydrophobic layer on the DNA that restricts access of H2O to the nucleobase radical cation.