NMR and molecular modeling evidence for a Gter dot A mismatch base pair in a purine-rich DNA duplex

Journal Article · Tue Jan 01 04:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.1.26· OSTI ID:5012927

Li, Ying; Wilson, W D ^[1]; Zon, G ^[2]

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1. Georgia State Univ., Atlanta (United States)
2. Applied Biosystems, Foster City, CA (United States)

{sup 1}H NMR experiments indicate that the oligomer 5{prime}-d(ATGAGCGAATA) forms an unusual 10-base-pair duplex with 4 G{center dot}A base pairs and a 3{prime} unpaired adenosine. NMR results indicate that guanoxine imino protons of the F{center dot}A mismatches are not hydrogen bonded but are stacked in the helix. A G{r arrow} I substitution in either G{center dot}A base pair causes a dramatic decrtease in duplex stability and indicates that hydrogen bonding of the guanosine amino group is critical. Nuclear Overhauser effect spectroscopy (NOESY) and two-dimensional correlated spectroscopy (COSY) results indicate that the overall duplex conformation is in the B-family. Cross-strand NOEs in two-dimensional NOESY spectra between a mismatched AH2 and an AH1{prime} of the other mismatched base pair and between a mismatched GH8 and GNH1 of the other mismatch establish a purine-purine stacking pattern, adenosine over adenosine and guanosine over guanosine, which strongly stabilizes the duplex. A computer graphics molecular model of the ususual duplex was constructed with G{center dot}A base pairs containing A-NH{sub 2} to GN3 and G-NH{sub 2} to AN7 hydrogen bonds and B-form base pairs on both sides of the G{center dot}A pairs (5{prime}-d(ATGAGC)). The energy-minimized duplex satisfies all experimental constraints from NOESY and COSY results. A hydrogen bond from G-NH{sub 2} of the mismatch to a phosphate oxygen is predicted.

• OSTI ID: 5012927
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:1; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AROMATICS
AZAARENES
BARYONS
COMPUTER GRAPHICS
DNA BASE TRANSITIONS
ELEMENTARY PARTICLES
FERMIONS
GUANOSINE
HADRONS
HETEROCYCLIC COMPOUNDS
MAGNETIC RESONANCE
MATHEMATICAL MODELS
MOLECULAR MODELS
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
NUCLEONS
NUCLEOSIDES
NUCLEOTIDES
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OVERHAUSER EFFECT
PROTONS
PURINES
RESONANCE
RIBOSIDES