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Our
primary research tool is multidimensional, multinuclear nuclear
magnetic resonance (NMR) spectroscopy. These techniques are
used to determine the three-dimensional structures of DNA
and RNA oligonucleotides, to investigate their interactions
with various proteins and drugs, and to study nucleic acid
folding.
Much
of our research is on unusual nucleic acid structures. These
include DNA and RNA triplexes and quadruplexes and aptamers.
Triplexes are formed by binding of a third strand of DNA or
RNA in the major groove of Watson-Crick duplex DNA.
Triplexes
are of interest both for their potential use as therapeutic
agents to repress gene expression and their proposed formation
in vivo as H-DNA. Quadruplexes are formed when four
guanine-rich strands associate via formation of Hoogsteen
bonded G-quartets. Formation of quadruplexes has been proposed
for the G-rich 3' single strand overhangs of telomeres, immunoglobulin
switch regions, and dimerization of HIV genomic RNA. Aptamers
are DNA or RNA ligands which have been selected from a random
pool of oligonucleotides for their ability to bind a specific
substrate. An example is a DNA 15mer which binds to and inhibits
thrombin.
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