Photodynamic Inhibition of E. coli DNA Polymerase I by 8-MOP and UV-A Irradiation

Abstract

Structure-reactivity relationships in the redox-photosensitized reactions have been interpreted in terms of electronic and steric properties of the dimers. The reactive syn dimers have the structures capable of through-bond interactions between the n orbitals of N(1) and N(1') involving the C(6) -C(6') bond; such interactions are structurally impossible for the unreactive anti dimers. When S` forms a nr complex with a syn, dimer, the positive charge should develop, even in part, on the side of the dimer because of the through-bond interactions (see Figure 2), leading to weakening of the C(6) C(6') bond. Therefore, the splitting process from [S PyOPy]+j should be strongly affected by the degrees of steric repulsion as well, because bond splitting can be assisted by repulsions between the substituents. It can thus be understood why redox photosensitization reveals high substrate-selective features unlike quinoneor uranyl ion-photosensitized reactions, which unselectively occur via the discrete cation radical of PyOPy. Some biological inferences can be made on the basis of these findings. The photosensitizing site of PR enzyme would contain a chemical species capable of developing a partial positive charge on pyrimidine dimer upon photoexcitation. According to this mechanism, substrate selectivities of PR would be almost steric. Photodynamic Inhibition of E. coli DNA Polymerase I by 8-MOP and UV-A Irradiation