title: Energy minimized structures of carcinogen-DNA adducts: 2-acetylaminofluorene and 2-aminofluorene.
abstract: Energy minimized structures of DNA modified by the aromatic amines 2-acetylaminofluorene (AAF) and 2-aminofluorene (AF), for which no experimental atomic resolution data exist, are presented. These have been computed with a new molecular mechanics program specifically designed to define distortions imposed by such adducts, and employing a rational strategy for searching the conformation space of a DNA molecule with covalently linked carcinogen. In alternating G-C sequences, the AAF adduct prefers to reside at the exterior of an undeformed Z-helix. It can also induce base displacement with attendant denaturation and helix bending in sequences that disfavor the Z form, but undeformed B helices are excluded. The AF adduct, by contrast, prefers the major groove of an unperturbed B-helix, but can also induce carcinogen-base stacking in single stranded regions of the DNA, such as at the replication fork. The different biological properties of these two adducts may be related to their distinct
authors.affiliation: Health and Safety Research Division, Oak Ridge National Laboratory, TN 37831.
authors.forename: B E
authors.initials: BE
authors.lastname: Hingerty
authors.forename: S
authors.initials: S
authors.lastname: Broyde
mesh_terms: D015073:2-Acetylaminofluorene; D002273:Carcinogens; D004247:DNA; D004735:Energy Transfer; D005449:Fluorenes; D015394:Molecular Structure; D009690:Nucleic Acid Conformation
chemical_list: D002273:Carcinogens; D005449:Fluorenes; C012177:2-aminofluorene; D004247:DNA; D015073:2-Acetylaminofluorene