Structure and properties of hydroxyl radical modified nucleic acid components: pairing properties of 2-hydroxyadenine and 8-oxoadenine

Abstract

Miscoding potential of 2-OH-adenine and 8-oxo-adenine was estimated on the basis of gradient geometry optimisation. Two most stable tautomers of each adenine derivative were used for dimer construction. Results of calculations allow concluding that adenine modified at C 2 position may form stable pairs with all four standard DNA bases. Both keto and enol tautomers may be involved in such pairs. The most preferred pairs of 2-OH-adenine are ones with guanine and cytosine. Most favourable pairs of 2-oxo-adenine are those with guanine and thymine. These pairs are more stable than standard A–T pair which suggests the significant potential miscoding character of this adenine derivative. The 8-oxo-adenine is also able to form stable pairs with guanine, cytosine and thymine. However, the stabilisation energies are less or equal to standard AT pair. Thus, the mispairing properties of 8-oxo-adenine are much less pronounced than for 2-OH-A. The water solvent effects leading to significant reduction of the pairs stabilities for all studied dimers is taken into account.