O sup 6 -ethylguanine carcinogenic lesions in DNA: An NMR study of O sup 6 etGter dot T pairing in dodecanucloetide duplexes
- Columbia Univ., New York, NY (USA)
High-resolution two-dimensional NMR studies are reported on the self-complementary d-(C1-G2-C3-{und O{sup 6}etG4}-A5-G6-C7-T8-{und T9}-G10-C11-G12) duplex (designated O{sup 6}etG{center dot}T 12-mer) containing two symmetrically related O{sup 6}etG{center dot}T lesion sites located four base pairs in from either end of the duplex. Parallel studies were undertaken on a related sequence containing O{sup 6}meG{center dot}T lesion sites (designated O{sup 6}meG{center dot}T 12-mer) in order to evaluate the influence of the size of the alkyl substituent on the structure of the duplex and were undertaken on a related sequence containing G{center dot}T mismatch sites (designated G{center dot}T 12-mer duplex), which served as the control duplex. The exchangeable and nonexchangeable proton and the phosphorus nuclei have been assigned from an analysis of two-dimensional nuclear Overhauser enhancement (NOE) and correlated spectra of the O{sup 6}etG{center dot}T 12-mer, O{sup 6}meG{center dot}T 12-mer, and G{center dot}T 12-mer duplexes in H{sub 2}O and D{sub 2}O solutions. The distance connectivities observed in the NOESY spectra of the O{sup 6}alkG{center dot}T 12-mer duplexes establish that the helix is right-handed and all of the bases adopt an anti conformation of the glycosidic torsion angle including the O{sup 6}alkG4 and T9 bases at the lesion site. These observations establish that the O{sup 6}alkG4 and T9 residues are stacked into the duplex and that the O{sup 6}CH{sub 3} and O{sup 6}CH{sub 2}CH{sub 3} groups of O{sup 6}alkG4 adopt a syn orientation with respect to the N{sup 1} of the alkylated guanine. Since the O{sup 6}-alkyl group adopts a syn orientation, the separation between the O{sup 6} of O{sup 6}alkG4 and the O{sup 4} of T9 in the major groove is increased, preventing the formation of a short hydrogen bond between the N{sup 1} ring nitrogen of O{sup 6}alkG4 and the imino proton of T9.
- OSTI ID:
- 5432900
- Journal Information:
- Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:15; ISSN 0006-2960; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ALKYLATION
AMINES
AROMATICS
AZAARENES
AZINES
BARYONS
CARCINOGENESIS
CHEMICAL REACTIONS
CHEMICAL SHIFT
DNA
ELEMENTARY PARTICLES
FERMIONS
GUANINE
HADRONS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MOLECULAR STRUCTURE
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEI
NUCLEIC ACIDS
NUCLEONS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OVERHAUSER EFFECT
PATHOGENESIS
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PROTONS
PURINES
PYRIMIDINES
RESONANCE
SPECTRA
STABLE ISOTOPES
THYMINE
URACILS