The impact of energy related pollutants on chromosome structures. Final performance report, May 1, 1987--April 30, 1992

This project addressed the sequence selectivities of DNA binding by intercalating agents. Methods analogous to chemical DNA sequencing were developed to quantitatively investigate sequence selectivities of DNA binding of several DNA intercalators including benzo(a)pyrene diol epoxides, ethidium, copper-phenanthroline complexes, and the anticancer drug actinomycin D. Computer programs were developed to extract sequence selectivities from large data sets. A photoaffinity analog approach was validated for determining the sequence selectivities of ethidium and actinomycin D. Several `non-traditional` binding sites were identified for each ligand examined. Actinomycin D was shown to bind single stranded DNA, as well as double stranded DNA, with high affinity and sequence selectivity. All of the compounds studied were intercalators, but they differ significantly in side chain complexity