Nuclear magnetic resonance solution structure of an undecanucleotide duplex with a complementary thymidine base opposite a 10R adduct derived from trans addition of a deoxyadenosine N6-amino group to (-)-(7R,8S,9R,10S)-7,8-dihydroxy- 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.
The solution structure of a modified undecamer duplex containing (-)-(7R,8S,9R,10S)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a] pyrene covalently bonded through trans ring opening at C10 of the epoxide by the N6-amino group of deoxyadenosine (dA) was studied. This diol epoxide 1 diastereomer has the benzylic 7-hydroxyl group and the epoxide oxygen cis. The modified nucleotide residue has R chirality at C10 of the hydrocarbon (10R adduct). The undecamer duplex d(C1G2G3T4C5A*6C7G8A9G10G11).d(C12C13T14C15G16T17G18A19C2 0C21G22) has a complementary T opposite the modified dA (dA*6 is the modified dA). Exchangeable and nonexchangeable proton assignments were made using 2D TOCSY, NOESY, and water/NOESY NMR spectroscopy. The hybrid complete relaxation matrix program MORASS was used to generate NOESY distance constraints for iterative refinement using distance-restrained molecular dynamics calculations. The refined structure showed the hydrocarbon intercalated from the major groove between dA*6-T17 and dC5-dG18 base pairs. The modified dA*6 was in the normal anti configuration and showed Watson-Crick base pairing to T17 opposite. The chemical shifts of the hydrocarbon protons and the unusual shifts of sugar protons were accounted for by the intercalated orientation of the hydrocarbon.
Schurter
E J
EJ
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
Sayer
J M
JM
Oh-hara
T
T
Yeh
H J
HJ
Yagi
H
H
Luxon
B A
BA
Jerina
D M
DM
Gorenstein
D G
DG
D001482:Base Composition; D001483:Base Sequence; D001580:Benzopyrenes / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D003839:Deoxyadenosines / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011522:Protons; D012996:Solutions; D013816:Thermodynamics
D001580:Benzopyrenes; D002273:Carcinogens; D018736:DNA Adducts; D003839:Deoxyadenosines; D009838:Oligodeoxyribonucleotides; D011522:Protons; D012996:Solutions; C039385:7,8-dihydroxy-9,10-epoxy-8-methyl-7,8,9,10-tetrahydrobenzo(a)pyrene