Coding and conformational properties of oligonucleotides modified with the carcinogen N-2-acetylaminofluorene.

The present studies were undertaken to determine the mechanism by which attachment of the carcinogen N-2-acetylaminofluorene to guanosine residues in nucleic acids distors their structure and function. Oligonucleotides were modified with N-acetoxy-2-acetylaminofluorene, repurified, and their base compositions analyzed. Evidence is presented that acetylaminofluorene residues bound to guanosines in GpUpU, ApApG, or poly (U,G) inactivates their function in codon recognition. Circular dichroism spectra suggest that this is caused by gross conformational changes in these compounds involving both a rotation about the glycosidic bond of guanosine residues bearing N-2-acetylaminofluorene, as well as stacking interactions between the drug and bases adjacent to the substituted guanosine.