NMR solution studies of covalent carcinogenic adducts and helical lesions in DNA
Oligodeoxyribonucleotide duplexes containing carcinogenic lesions and helical errors were probed by proton and phosphorus nuclear magnetic resonance (NMR). Homonuclear correlated (COSY) and nuclear Overhauser effect (NOESY) spectroscopy were utilized to assign the majority of the proton resonances to specific residues in each duplex. Heteronuclear ({sup 31}P-{sup 1}H) correlation spectroscopy was used to assign the phosphorus resonances to specific phosphodiester backbone positions in each helix. The NOE, spin-spin coupling, and chemical shift data were interpreted qualitatively, providing information on hydrogen-bonding, glycosidic torsion angles, sugar puckers, stacking interactions, helix stability, and phosphodiester backbone conformation. Our studies have analyzed the effects of flanking base pairs and the type of extra-base (purine or pyrimidine) on the stacking behavior of an extra-base at a bulge site in self-complementary duplexes. The base-pairing properties of covalent carcinogenic O-alky lesions of purine and pyrimidine bases, specifically, O{sup 4}-methyl thymidine (O{sup 4}meT), O{sup 6}-methyl guanosine (O{sup 6}meG), and O{sup 6}-ethyl guanosine (O{sup 6}etG), were identified. The other helical errors studied were synthetic analogs of apurinic/apyrimidinic (AP) sites opposite adenosine in the center of otherwise identical nonamer duplexes.
- Research Organization:
- Columbia Univ., New York, NY (USA)
- OSTI ID:
- 7117886
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DNA ADDUCTS
NMR SPECTRA
NUCLEOTIDES
MOLECULAR STRUCTURE
CARCINOGENS
CHEMICAL SHIFT
COVALENCE
DNA
NUCLEAR MAGNETIC RESONANCE
OVERHAUSER EFFECT
PHOSPHORUS 31
PROTONS
TRACER TECHNIQUES
ADDUCTS
BARYONS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
NUCLEI
NUCLEIC ACIDS
NUCLEONS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
RESONANCE
SPECTRA
STABLE ISOTOPES
550201* - Biochemistry- Tracer Techniques