Conformation of 2‐aminofluorene‐modified DNA

Minimized potential‐energy calculations were performed to determine the conformation of the 2‐aminofluorene (AF) adduct to dCpdG at guanine C‐8. The AF adduct has many low‐energy conformers in both the anti and the syn domains of the guanine. This is in contrast with the acetylated adduct, (AAF), which greatly prefers the syn domain. Two types of low‐energy guanine anti‐conformations were obtained: (1) conformers that preserve guanine–cytidine stacking and (2) conformers with fluorene–cytidine stacking. Of special importance are conformers with ω′,ω,ψ = g⁻, g⁻, g⁺, characteristic of normal A‐ or B‐helices, which are found in both groups. No conformers of this type were obtained for the acetylated AAF adduct. The guanine–cytidine stacked from with this conformation can be incorporated in the B‐helix without any distortion, with the carcinogen situated at the helix exterior. The fluorene in this model can slide into the helix to yield a fluorene–cytidine stacked minimum‐energy conformation. This requires no denaturation, although one base pair is unstacked and the helix axis is bent. Low‐energy syn‐conformations, similar to those obtained for the AAF adduct, were also computed. These were either guanine‐cytidine stacked or fluorene–cytidine stacked. The syn froms are less likely to be observed in larger DNA polymers of the adduct, since they cause more distortion than the anti‐conformations. However, they might well be observed in crystals of small subunits, and they should contribute significantly to the population in solution.