B-Z transition in methylated DNA : a quantum-chemical study

On the basis of modified neflect of differntial overlap (MNDO) quantum-chemiocal calculations on nucleoside systems, we descrive the effect of methylation on the energies calculated for the rotation around the glycosidic C(1')-N bond. We found a high anti-syn activation energy in the case of the pyrimidine nucleosides C and m5C, Whereas for the purine nucleosides G, m6G, m7 and m8 only moderate anti-syn energetic barriers were claculated. This result is conssitent with the experimentally observed preference for d(G-C)3 and d(G-m5C)3 duplexes to adopt Z-DNA stuctures, in which the syn conformation of guanine is favoured. Enhanced anti-syn activation energy with respect to the unmethylated derivative was calculated in the cases of m5G. This result is rationalized on the basis of steric and electronic factors. In addition, an increased stabilization of the syn conformer due to selective methylation of guanine was calculated. The data obtained are in good corrspondence with the experimentally observed B-Z transition iun synthetic methylated DNA duplexes with alternating dC-dG sequence. Our work concerning the initiating step in the B-Z transistion which involves rotation around the C(4')-C(5') bond induced by P(V) trigonal bipyramidal intermediates is discussed. In combination with the rotation around the glycosidic C(1')-N bond, it can be shown that the phosphate withinh thge dpC structure is selectively sctivated.