Base pair mismatches and carcinogen-modified bases in DNA: an NMR study of G x T and G x O/sup 4/meT pairing in dodecanucleotide duplexes

Journal Article · Tue Jan 12 00:00:00 EST 1988 · Biochemistry; (United States)

OSTI ID:5444653

Kalnik, M W; Kouchakdjian, M; Li, B F.L.; Swann, P F; Patel, D J

High-resolution two-dimensional NMR studies have been completed on the self-complementary d(C-G-C-G-A-G-C-T-T-G-C-G) duplex (designated G x T 12-mer) and the self-complementary d(C-G-C-G-A-G-C-T-O/sup 4/meT-G-C-G) duplex (designated G x O/sup 4/meT 12-mer) containing G x T and G x O/sup 4/meT pairs at identical positions four base pairs in from either end of the duplex. The exchangeable and nonexchangeable proton resonances have been assigned from an analysis of two-dimensional nuclear Overhauser enhancement (NOESY) spectra for the G x T 12-mer and G x O/sup 4/meT 12-mer duplexes in H/sub 2/O and D/sub 2/O solution. The guanosine and thymidine imino protons in the G x T mismatch resonate at 10.57 and 11.98 ppm, respectively, and exhibit a strong NOE between themselves and to imino protons of flanking base pairs in the G x T 12-mer duplex. The large upfield chemical shift of this proton relative to that of the imino proton resonance of G in the G x T mismatch or in G x C base pairs indicates that hydrogen bonding to O/sup 4/meT is either very weak or absent. This guanosine imino proton has an NOE to the OCH/sub 3/ group of O/sup 4/meT across the pair and NOEs to the imino protons of flanking base pairs. Taken together with data from the NMR of nonexchangeable protons, this shows that both G and O/sup 4/meT have anti-glycosidic torsion angles and are stacked into the duplex. Comparison of the intensity of the NOEs between the guanosine imino proton and the OCH/sub 3/ of O/sup 4/meT as well as other protons in its vicinity demonstrates that the OCH/sub 3/ group of O/sup 4/meT adopts the syn orientation with respect to N3 of the methylated thymidine. The authors propose an alternate base pairing mode stabilized by one short hydrogen bond between the 2-amino group of guanosine and the 2-carbonyl group of O/sup 4/met.

• Research Organization: Columbia Univ., New York, NY
• OSTI ID: 5444653
• Journal Information: Biochemistry; (United States), Vol. 27:1
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
59 BASIC BIOLOGICAL SCIENCES
GUANOSINE
CONFIGURATION INTERACTION
OLIGONUCLEOTIDES
NUCLEAR MAGNETIC RESONANCE
THYMINE
CHEMICAL SHIFT
NMR SPECTRA
OVERHAUSER EFFECT
PROTONS
AROMATICS
AZAARENES
AZINES
BARYONS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PURINES
PYRIMIDINES
RESONANCE
RIBOSIDES
SPECTRA
URACILS
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