| Abstract: |
The guanine base in DNA duplexes is a target for covalent adduct and crosslink formation with a range of mutagens and carcinogens. The structures of these DNA lesions have been elucidated by combining NMR and structure reconstruction methodologies on each adduct in a defined sequence context at the DNA oligomer level. Solution structures are available on benzo[a]pyrene diol epoxide, sterigmatocystin and aminofluorene adducts, intrastrand cis-platinum bifunctional adducts and interstrand mitomycin crosslinks. These structures define a range of DNA conformational perturbations at the lesion site and provide insights into the role of chiral functional groups on the carcinogen in determining its alignment along the DNA helix. These structures also exhibit a range of intermolecular stacking, hydrogen-bonding and hydrophobic interactions that stabilize the lesion-DNA interface. The structural data can be correlated with the available spectrum of mutational and carcinogenic activities associated with these lesions. © 1992. |
