SOLUTION CONFORMATION OF THE N-(DEOXYGUANOSIN-8-YL)AMINOFLUORENE ADDUCT OPPOSITE DEOXYINOSINE AND DEOXYGUANOSINE IN DNA BY NMR AND COMPUTATIONAL CHARACTERIZATION
P. Abuaf et al., SOLUTION CONFORMATION OF THE N-(DEOXYGUANOSIN-8-YL)AMINOFLUORENE ADDUCT OPPOSITE DEOXYINOSINE AND DEOXYGUANOSINE IN DNA BY NMR AND COMPUTATIONAL CHARACTERIZATION, Chemical research in toxicology, 8(3), 1995, pp. 369-378
Two-dimensional proton NMR and energy minimization computations have b
een employed to characterize the conformations of the N-(deoxyguanosin
-8-yl) aminofluorene adduct [(AF)G] positioned opposite deoxyguanosine
in one, and opposite deoxyinosine in another DNA undecamer duplex in
aqueous solution. The two oligomer duplexes used in this study are 11]
-[G12-G13-T14-A15-G16-X17-G18-A19-T20-G21-G22], where X17 was deoxyino
sine in one duplex and deoxyguanosine in another. The exchangeable and
nonexchangeable protons of the DNA are well resolved and narrow in th
e NMR spectra of the duplexes, and the base and sugar nucleic acid pro
tons were assigned by NOESY and COSY data sets. All nine of the nonexc
hangeable aminofluorene ring protons were also assigned for the duplex
that has deoxyinosine across from the modification site, and the (AF)
G;I structure was employed to model the (AF)G . G one. The NOE distanc
e restraints establish that the glycosidic torsion angle at (AF)G . 6
is syn. All other glycosidic torsion angles are anti, Watson-Crick typ
e A . T and G . C base pairing is intact throughout the duplex except
at the site of modification, and the helix maintains an overall B-DNA
conformation. The syn orientation at the (AF)G6 places the aminofluore
ne ring in the B-DNA minor groove in a conformation similar to that fo
und previously when the (AF)G was positioned opposite deoxyadenosine [
Norman et al. (1989) Biochemistry 28, 7462-7476].