Molecular aspects of methylated adenine in DNA : a quantum-chemical study

On the basis of modified neglect of differential overlap (MNDO) quantum-chemical calculations on nucleoside systems, the effect of methylation of adenine on the anti-syn equilibrium is described and an increased stabilization of the syn conformer, due to selective methylation, is calculated. A moderate anti-syn activation energy has been found in the case of dm3A, dm6A and dm7A, whereas for dm8A a considerably higher anti-syn energetic barrier exists. The results are combined with stereo model studies and related to biological data. With respect to restriction-modification systems, special attention is given to the computed stereochemical freedom of the methyl group in dm6A, with a significant preference for the syn conformation in dm8A being found, leading to the suggestion that, out of the various methylated structures studied, only alternating d(m8A-T) stretches are able to adopt a Z-DNA duplex.