This project seeks continuing support for an experimental investigation of the basis of the remarkable apparent sequence selectivity shown by 9-amino acridine and the 2-nitro fluorene in reverting his frameshift mutations in the Ames test. 1H, 31P and 19F NMR studies of the complexes between these agents and oligonucleotide duplexes of defined sequence will be performed to define the structural energetic and dynamic characteristics of the interaction in vitro. We have found a suggestive structural difference between intercalated complexes between 9AA-dGpC and 9AA-dGpG/dCpC, which provides a possible basis for the recognition. The corresponding detailed investigation of 2NF has not been done. Experiments using paramagnetic probes, bifunctional drugs as well as nonclassical duplex DNA structures are also proposed, as in an investigation of model covalent adducts at the oligonucleotide level.
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