B-Z transition in methylated DNA. A quantum-chemical study.
On the basis of modified neglect of differential overlap (MNDO) quantum-chemical calculations on nucleoside systems, we describe 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, m7G and m8G only moderate anti-syn energetic barriers were calculated. This result is consistent with the experimentally observed preference for d(G-C)2, d(G-C)3 and d(G-m5C)3 duplexes to adopt Z-DNA structures, 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 m5C and m8G. 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 correspondence with the experimentally observed B-Z transition in synthetic methylated DNA duplexes with alternating dC-dG sequence. Our work concerning the initiating step in the B-Z transition 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 within the dpC structure is selectively activated.
D055598:Chemical Phenomena; D002621:Chemistry; D003596:Cytosine / Q000032:analysis; D004247:DNA; D006147:Guanine / Q000032:analysis; D008745:Methylation; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
D006147:Guanine; D003596:Cytosine; D004247:DNA