Two-Dimensional ¹H and ³¹P NMR Spectra of a Decamer Oligodeoxyribonucleotide Duplex and a Quinoxaline ([MeCys³, MeCys⁷]TANDEM) Drug Duplex Complex

Authors

Robert Powers, University of Nebraska - LincolnFollow
Richard K. Olsen, Utah State University
David G. Gorenstein, Purdue University

Date of this Version

1989

Citation

Published in Journal of Biomolecular Structure and Dynamics 7:3 (1989), pp. 515–556

Comments

Copyright © 1989 Adenine Press. Published by Taylor & Francis. Used by permission.

Abstract

Assignment of the ¹H and ³¹P NMR spectra of a decamer oligodeoxyribonucleotide duplex, d(CCCGATCGGG), and its quinoxaline ([MeCys³, MeCys⁷]TANDEM) drug duplex complex has been made by two-dimensional ¹H-¹H and heteronuclear ³¹P-1H correlated spectroscopy. The ³¹P 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 ³¹P resonance occurs. While the ³¹P chemical shifts show sequence-specific variations, they also do not generally follow the Calladine “rules” previously demonstrated. ³¹P 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, [MeCys³, MeCys⁷]TANDEM, is generally expected to bind to duplex DNA by bis-intercalation, only small ³¹P chemical shift changes are observed upon binding the drug to duplex d(CCCGATCGGG). Additionally, only small perturbations in the ¹H 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.