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Title: O sup 6 -ethylguanine carcinogenic lesions in DNA: An NMR study of O sup 6 etGter dot C pairing in dodecanucleotide duplexes

The pairing of O{sup 6}etG with C located four base pairs in from either end of the self-complementary d(C1-G2-C3-{und O{sup 6}etG4}-A5-G6-C7-T8-{und C9}-G10-C11-G12) duplex (designated O{sup 6}etG{center dot}C 12-mer) has been investigated from an analysis of proton and phosphorus two-dimensional NMR experiments. The structural consequences of increasing the alkyl group size were elucidated from a comparative study of the pairing of O{sup 6}meG4 with C9 in a related sequence (designated O{sup 6}meG{center dot}C 12-mer). The NMR parameters for both O{sup 6}alkG-containing dodecanucleotides are also compared with those of the control sequence containing G4{center dot}C9 base pairs (designated G{center dot}C 12-mer). The NOE cross-peaks detected in the two-dimensional NOESY spectra of the O{sup 6}alkG{center dot}C 12-mer duplexes in H{sub 2}O solution establish that the O{sup 6}etG4/O{sup 6}meG4 and C9 bases at the lesion site stack into the helix between the flanking C3{center dot}G10 and A5{center dot}T8 Watson-Crick base pairs. The observed NOEs between the amino protons of C9 and the CH{sub 3} protons of O{sup 6}alkG4 establish a syn orientation of the O{sup 6}-alkyl group with respect to the N{sup 1} of alkylated guanine. A wobble alignment of the O{sup 6}alkG4{center dot}C9 base pair stabilized by two hydrogen bonds, one between themore » amino group of C9 and N{sup 1} of O{sup 6}alkG and the other between the amino group of O{sup 6}alkG and N{sup 3} of C9, is tentatively proposed on the basis of the NOEs between the amino protons of C9 at the lesion site and the imino protons of flanking Watson-Crick base pairs.« less
Authors:
; ; ;  [1]
  1. (Columbia Univ., New York, NY (USA))
Publication Date:
OSTI Identifier:
5353410
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; (USA); Journal Volume: 28:15
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CYTOSINE; ALKYLATION; DNA; NUCLEAR MAGNETIC RESONANCE; GUANINE; CARCINOGENESIS; CHEMICAL SHIFT; HEAVY WATER; MOLECULAR STRUCTURE; OVERHAUSER EFFECT; PHOSPHORUS 31; PROTONS; AMINES; AROMATICS; AZAARENES; AZINES; BARYONS; CHEMICAL REACTIONS; ELEMENTARY PARTICLES; FERMIONS; HADRONS; HETEROCYCLIC COMPOUNDS; HYDROGEN COMPOUNDS; HYDROXY COMPOUNDS; ISOTOPES; LIGHT NUCLEI; MAGNETIC RESONANCE; NUCLEI; NUCLEIC ACIDS; NUCLEONS; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; OXYGEN COMPOUNDS; PATHOGENESIS; PHOSPHORUS ISOTOPES; PURINES; PYRIMIDINES; RESONANCE; STABLE ISOTOPES; WATER 550201* -- Biochemistry-- Tracer Techniques