2-Aminofluorene modified DNA duplex exists in two interchangeable conformations

One- and two-dimensional NMR shows that the carcinogen 2-aminofluorene exists in two unique, interchangeable conformations when covalently bound to a model human c-H-ras1 proto-oncogene codon 61 oligomer duplex. In one conformation the 2-aminofluorene moiety protrudes out of the major groove leaving the Watson-Crick base pairing of the cytosine and 2-aminofluorene-guanine bases intact, consistent with the ability of replicating enzymes to bypass the lesion and correctly incorporate cytosine. The second form of the modified oligomer duplex may be representative of a pre-mutagenic conformation in that the 2-aminofluorene moiety is stacked within the DNA helix, disrupting base pairing between the 2-aminofluorene-modified guanine and its complementary cytosine.