Abstract
This chapter reviews the conformational changes in nucleic acids associated with noncovalent binding and intercalation with certain drugs and carcinogens. Conformational changes associated with covalent modification by chemical carcinogens can be studied either with low-molecular-weight oligonucleotides, which mimic relatively well the situation in macromolecules, or with polymeric nucleic acids as model compounds. X-Ray diffraction and a variety of spectral techniques have provided extensive information on the conformations of nucleosides, oligonucleotides, and single- and double-strand nucleic acids. A common feature of most chemical carcinogens is that they are metabolically converted to electrophilic forms that react with nucleophilic centers in nucleic acids and proteins. The base displacement model predicts that 2-acetylaminofluorene (AAF) modification of double-stranded nucleic acids should produce a localized denaturation at the site of AAF modification. The base displacement model enables one to make several predictions concerning the functional aspects of the modified nucleic acid.
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