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Kanvah and Schuster (J. Am. Chem. Soc. 2004, 126, 7341) have recently questioned whether 5-MeC substituted in DNA can affect radical cation hopping through DNA. Their measurements indicate that the answer may be no. The markers in their experiments are strand cleavage at G sites. Oxidation of 5-MeC provides a stable allyl radical that would not lead to a strand break, so it is not clear how these results test the hypothesis that 5-MeC is a locus of oxidative damage in DNA.
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Reviews of the X-ray crystallographic structures of the nucleic acid bases have led to the conclusion that "The similarity between the dimensions of the standard residues and the average dimensions observed in the crystal structures suggest that the assumption of exact base planarity is justified" (Taylor, R.; Kennard, O. J. Am. Chem. Soc. 1982, 104, 3209). Widely used empirical force fields such as AMBER and CHARMM also assume planar and rather rigid amino groups. New parametrization of the Cornell force field allows for partial sp3 hybridization of the amino nitrogen ( Rajacek, F.; Kubar, T.; Hobza, P. J. Comput. Chem. 2003, 24, 1891.).
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