Chemistry Reference
In-Depth Information
Figure 11.9
Comparative models of B- (left) and A-form (right) nucleic acids. The major
and minor grooves are labelled
In order to make a direct comparison with the results obtained with DNA, the
binding of the two enantiomers of [{Ru(Me
2
bpy)
2
}
2
( m - bpm)]
4+
to the RNA analogue
of the adenine bulge-containing DNA sequence d(CCG
A
GAATTCCGG)
2
, and the
corresponding bulge-free control RNA dodecanucleotide, were examined.
118
Both
enantiomers bound the control RNA duplex weakly (
K
= 1
10
3
M
− 1
), but bound
the r(CCG
A
GAAUUCCGG)
2
structure with considerably greater affi nity
(
K
= 6
×
10
4
M
− 1
). From NOESY spectra, it was established that the ruthenium
complex did selectively bind at the bulge site. A binding model that was consistent
with all the NMR was obtained that demonstrated that D
D - [{Ru(Me
2
bpy)
2
}
2
( m -
bpm)]
4+
could effectively associate at the bulge site in the RNA minor groove. It
was proposed that the insertion of the bulge into the tridecanucleotide formed a
metal complex binding pocket by partially unwinding the duplex at the unpaired
adenine. This perturbation to the RNA duplex caused a reduction in the curvature
of the minor groove that may have aided the binding of the ruthenium complex.
Alternatively, the minor groove structure at the bulge site may be more fl exible, due
to the reduced thermodynamic stability produced by the unpaired adenine, thereby
allowing a better induced-fi t binding site. The results of the study demonstrated that
inert dinuclear ruthenium complexes have excellent potential as probes for nondu-
plex RNA structures, in a similar manner to that previously established for DNA.
×
11.3.6 Dinuclear Ruthenium Complexes with Flexible Ligands
Although the dinuclear ruthenium complexes that are bridged by rigid linking
ligands, such as bpm and HAT, exhibit relatively strong binding to nonduplex DNA
