Modification of ribonucleic acid by chemical carcinogens. IV. Circular dichroism and proton magnetic resonance studies of oligonucleotides modified with N-2-acetylaminofluorene

The conformational properties of various oligonucleotides modified with the chemical carcinogen N-2-acetylaminofluorene have been investigated utilizing circular dichroism, proton magnetic resonance spectroscopy and computer-generated molecular models. Introduction of the carcinogen, specifically and covalently, at the C-8 position of guanosine residues results in dramatic changes in the ciruclar dichroism spectra of the oligonucleotides. The attachment of N-2-acetylaminofluorene also causes large higher-field shifts for the proton resonances of fluorene and bases adjacent to a modified guanosine residue. These results, together with substantial supporting evidence, show that the covalent binding of N-2-acetylaminofluorene causes important changes in the conformational properties of oligonucleotides in aqueous solution. The major changes include rotation of the guanine base around the glycosidic linkage and the intramolecular stacking of fluorene with an adjacent base. A computer-displayed model of a carcinogen-modified dinucleotide illustrating these effects is presented. The specific conformational changes noted for the oligonucleotides could clearly disrupt the normal biological activity of similarly modified naturally occurring nucleic acids.