Base pair mismatches and carcinogen-modified bases in DNA: an NMR study of A x C and A x O/sup 4/meT pairing in dodecanucleotide duplexes
Structural features of A x C mismatches and A x O/sup 4/meT pairs in the interior of oligodeoxynucleotide duplexes have been investigated by high-resolution two-dimensional proton NMR spectroscopy on the self-complementary d(C-G-C-A-A-G-C-T-C-G-C-G) duplex (designated A x C 12-mer) and the self-complementary d(C-G-C-A-A-G-C-T-O/sup 4/meT-G-C-G) duplex (designated Ax O/sup 4/met 12-mer) containing A x C and A x O/sup 4/meT pairs at identical positions four base pairs in from either end of the duplex. Proton NMR shows that there are similar pH-dependent changes in the structure in the A x C 12-mer and A x O/sup 4/meT 12-mer duplexes. The studies have focused on the low-pH (pH 5.5) conformation where high-quality two-dimensional NOESY data sets were collected from the exchangeable and nonexchangeable protons in these duplexes. The spectral parameters for the A x C 12-mer and the A x O/sup 4/meT 12-mer duplexes were very similar. Both structures are right-handed double helices with all the bases adopting the normal anti configuration about the glycosidic bond. The same atoms are involved in hydrogen-bond pairing for the A x C mismatch and the A x O/sup 4/meT pair, and these pairs have similar spatial relationship to flanking base pairs. The comparative NMR study on the A x C 12-mer and A x O/sup 4/meT 12-mer duplexes demonstrates wobble pairing for the A x O/sup 4/meT lesion. The authors can monitor the amino protons of A in the A x C mismatch and the A x O/sup 4/meT pair in the low-pH spectra (pH 5.5-6.0), providing additional markers at the modifications sites. Further, the distance-dependent NOE measurements establish that the OCH/sub 3/ group of O/sup 4/meT adopts a syn orientation with respect to N3 of the base and is directed toward the A on the partner strand in the A x O/sup 4/meT pair. The lateral displacement of the bases in the wobble pairing allows the OCH/sub 3/ group in the syn orientation to be accommodated in the helix.
- Research Organization:
- Columbia Univ., New York, NY
- OSTI ID:
- 5436504
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 27:1; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ADENINES
AMINES
ANTIMETABOLITES
AROMATICS
AZAARENES
AZINES
BARYONS
CARCINOGENS
CHEMICAL SHIFT
CYTOSINE
DRUGS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HETEROCYCLIC COMPOUNDS
MAGNETIC RESONANCE
MOLECULAR STRUCTURE
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PH VALUE
PROTONS
PURINES
PYRIMIDINES
RESONANCE
SPECTRA