TOXI 133 |
| Aristolochic acids (1) are nitropolyaromatic compounds found in herbs of Aristolochia family, which are used extensively in traditional medicine. Metabolic activation of aristolochic acids produces a highly reactive nitrenium intermediate that induces DNA lesions, mostly via reaction at the guanine N2 or the adenine N6 (2). As a result, aristolochic acids are one of the most active naturally occurring carcinogens. We present the NMR structure of DNA duplex containing the aristolactam II attached to the adenine N6. Our data show that the lesion significantly changes a conformation of the modified dA-dT base pair. The arictolactam moiety wedges into the base pair stack displacing the complementary thymine outside a helix. In contrast, the modified adenine retains its anti-conformation remaining stacked between flanking bases. We will discuss the implications of the structure for AAII toxicity and lesion repair.
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General Papers
1:00 PM-4:45 PM, Wednesday, August 22, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |
