Two-dimensional 1H and 31P NMR spectra of a decamer oligodeoxyribonucleotide duplex and a quinoxaline ((MeCys3, MeCys7)TANDEM) drug duplex complex
- Purdue Univ., West Lafayette, IN (USA)
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 non-intercalative 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.
- OSTI ID:
- 7045660
- Journal Information:
- Journal of Biomolecular Structure and Dynamics; (USA), Journal Name: Journal of Biomolecular Structure and Dynamics; (USA) Vol. 7:3; ISSN 0739-1102; ISSN JBSDD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BARYONS
BIOCHEMICAL REACTION KINETICS
CHEMICAL SHIFT
DNA
ELEMENTARY PARTICLES
FERMIONS
HADRONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAGNETIC RESONANCE
MAMMALS
MICE
MOLECULAR STRUCTURE
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEIC ACIDS
NUCLEONS
ODD-EVEN NUCLEI
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PROTONS
REACTION KINETICS
RESONANCE
RODENTS
SPECTRA
STABLE ISOTOPES
THERMODYNAMICS
VERTEBRATES