Identifying hydrogen bond alignments in multistranded DNA architectures by NMR.
NMR studies of nucleic acids have benefited tremendously from the discovery of trans-hydrogen-bond scalar coupling constants, which have enabled direct determination of N-H...N and N-H...O=C hydrogen bonds using a combination of (2h)J(NN)-, (4h)J(NN)-, and (3h)J(NC)-based spectroscopy. This is especially true of multistranded DNA architectures containing intricate hydrogen-bonded networks mediated primarily through mismatched base pairing, which often resist identification by posing serious technical, spectroscopic, and physicochemical challenges. In this Account, we present a suite of NMR pulse sequences that have been developed in our laboratory to address these issues. We demonstrate the utility of these methods for identifying hydrogen bonds in two quadruplex DNA structures, containing triad, tetrad, and hexad motifs involving Watson-Crick, G.G and sheared G.A mismatch base pairing.
Majumdar
Ananya
A
Cellular Biochemistry and Biophysics Department, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. majumdar@sbnm1.mskcc.org
Patel
Dinshaw J
DJ
D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*
D004247:DNA