Effect of /V-2-Acetylaminofluorene Modification on the Conformation of Nucleic Acids1

The present study extends this analysis to the effects of drug modification on DNA, reovirus RNA, ribosomal RNA, and polyadenylic acid. The rate and extent of reaction of denatured DNA with the drug were found to be 2 to 3 times greater than with native DNA; a high ionic environment which is known to stabilize nucleic acid secondary structure decreased the rate and extent of nucleic acid modification. Drug-modified native DNA exhibited a decrease in thermal stability and intrinsic viscosity and a tendency to elute at lower salt concentration from a hydroxyapatite column. The susceptibility of double-stranded reovirus RNA to ribonuclease digestion was increased by modification with the drug, and modified Escherichia coli ribosomal RNA was impaired in its ability to hybridize to homologous DNA. These findings indicate that modification of highmolecular-weight double-stranded nucleic acids produces localized regions of denaturation, a finding consistent with the base displacement model. In addition to covalent binding of the drug to nucleic acids, extensive noncovalent binding to native DNA and polyadenylic acid was observed.