Two-Dimensional¹H and³¹P NMR Spectra of a Decamer Oligodeoxyribonucleotide Duplex and a Quinoxaline ([MeCys³, MeCys⁷]TANDEM) Drug Duplex Complex

Abstract

Assignment of the 1 H and 31 P NMR spectra of a decamer oligodeoxyribonucleotide duplex, d(CCCGATCGGG), and its quinoxaline ([MeCys 3 , MeCys 7 ]TANDEM) drug duplex complex has been made by two-dimensional 1 H-1 H and heteronuclear 31 P-1 H correlated spectroscopy. The 31 P chemical shifts of this 10 base pair oligonucleotide follow the general observation that the more internal the phosphate is located within the oligonucleotide sequence, the more upfield the 31 P resonance occurs. While the 31 P chemical shifts show sequence-specific variations, they also do not generally follow the Calladine "rules" previously demonstrated. 31 P NMR also provides a convenient monitor of the phosphate ester backbone conformational changes upon binding of the drug to the duplex. Although the quinoxaline drug, [MeCys 3 , MeCys 7 ]TANDEM, is generally expected to bind to duplex DNA by bis-intercalation, only small 31 P chemical shift changes are observed upon binding the drug to duplex d(CCCGATCGGG). Additionally, only small perturbations in the 1 H NMR and UV spectra are observed upon binding the drug to the decamer, although association of the drug stabilizes the duplex form relative to the other states. These results are consistent with a nonintercalative mode of association of the drug. Modeling and molecular mechanics energy minimization demonstrate that a novel structure in which the two quinoxaline rings of the drug binds in the minor groove of the duplex is possible.

2D1H and31P NMR Spectra and Distorted A-DNA-Like Duplex Structure of a Phosphorodithioate Oligonucleotide

“…In practice, the integrity of the AMBER database appears to have been well-maintained. The charges, geometry and other force field parameters for the dithiophosphate are listed in Table I. NOESY distance constraints were incorporated into this modified potential energy force field through addition of a pseudo-energy flatwell potential (33,34) to the MINMD module of AMBER. Energy minimization and molecular dynamics were carried out using this modified AMBER program.…”

Dynamics and relative stabilities of parallel- and antiparallel-stranded DNA duplexes

“…1H NMR and 31P NMR studies (Germann, 1989) show that ps-DNA exhibit large backbone flexibility. A large number of P NMR resonances suggest that many E and , dihedral angles can be sampled by the backbone (Powers, 1989(Powers, , 1990 Lankhorst, 1984). 2D NMR of the dA10C4T10 (van de Sande, 1988) hairpin has recently been reported (Zhow, 1993).…”