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 N-6-AMINO GROUP TO DROXY-9,10-EPOXY-7,8,9,10-TETRAHYDROBENZO[A]PYRENE
Ej. Schurter et al., 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 N-6-AMINO GROUP TO DROXY-9,10-EPOXY-7,8,9,10-TETRAHYDROBENZO[A]PYRENE, Biochemistry, 34(28), 1995, pp. 9009-9020
The solution structure of a modified undecamer duplex containing roxy-
9,10,-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene covalently bonded throug
h trans ring opening at C10 of the epoxide by the N-6-amino group of d
eoxyadenosine (dA) was studied. This diol epoxide 1 diastereomer has t
he benzylic 7-hydroxyl group and the epoxide oxygen cis. The modified
nucleotide residue has R chirality at C10 of the hydrocarbon (10R addu
ct). The undecamer duplex (C(1)G(2)G(3)T(4)C(5)A(6)C(7)G(8)A(9)G(10)G
(11)). (13)T(14)C(15)G(16)T(17)G(18)A(19)C(20)C(21)G(22)) has a comple
mentary T opposite the modified dA (dA6 is the modified dA). Exchange
able and nonexchangeable proton assignments were made using 2D TOCSY,
NOESY, and water/NOESY NMR spectroscopy. The hybrid complete relaxatio
n matrix program MORASS was used to generate NOESY distance constraint
s for iterative refinement using distance-restrained molecular dynamic
s calculations. The refined structure showed the hydrocarbon intercala
ted from the major groove between dA6-T17 and dC5-dG18 base pairs. Th
e modified dA6 was in the normal anti configuration and showed Watson
-Crick base pairing to T17 opposite. The chemical shifts of the hydroc
arbon protons and the unusual shifts of sugar protons were accounted f
or by the intercalated orientation of the hydrocarbon.