Chemistry Reference
In-Depth Information
ruthenium complex is approximately 16 Å long and 8.0 Å wide, while for canonical
form B-type DNA the width of the major and minor grooves are 11.6 Å and 6.0 Å,
respectively. Although the ruthenium complexes bound duplex DNA weakly, the
NMR results demonstrated that the D
D - and L
L - enantiomers interacted differently
with the dodecanucleotides used in the study, with the D
D - enantiomer having a
slightly higher affi nity.
Mononuclear polypyridyl ruthenium(II) complexes that bind DNA noninter-
calatively generally associate in the minor groove with a strong preference for A/T
rich sequences.
96
Distinctively, the stereoisomers of [{Ru(Me
2
bpy)
2
}
2
( m - bpm)]
4+
were
shown to bind d(CAATCCGGATTG)
2
at the central CCGG sequence and at the
CA/GT terminal residues, rather than at the expected A/T rich regions. As the minor
groove is particularly narrow at A/T rich sequences, it is probable that the relatively
bulky ruthenium complex could not be easily accommodated at the AAT/TTA sites.
Consequently, it was proposed that the ruthenium complex binds at the central
CCGG site, where the minor groove is more open, and at the terminal CA/GT site
where the minor groove would also be considerably widened due to the fraying of
the terminal base pair.
11.3.3 Interaction of Dinuclear Complexes with DNA Bulge Sequences
As the bulky ruthenium complexes only bound DNA where the minor groove was
relatively wide, it was proposed that they would bind DNA secondary structures
that contain a more open or fl exible groove with signifi cantly higher affi nity than
duplex DNA. This proposal was consistent with the results from Kirsch-De Mes-
maeker, Keene and coworkers,
97
who showed that [{Ru(phen)
2
}
2
( m - HAT)]
4+
(HAT = 1,4,5,8,9,12 - hexaazatriphenylene; Figure 11.2 b) binds partially - denatured
DNA signifi cantly more strongly than duplex DNA. One example of an open DNA
structure is a sequence that contains a so-called 'bulge' - the inclusion of one or
more bases on one strand that have no base(s) on the complementary strand with
which to form a base pair (see Figure 11.5). DNA bulge sites can be created during
recombination between imperfectly homologous sequences, and are thought to play
an important role in frame-shift mutagenesis and be specifi c recognition sites for
some DNA binding proteins. Consequently, there is considerable interest in devel-
oping small molecules that target bulge sites.
NMR experiments demonstrated that D
D - [{Ru(Me
2
bpy)
2
}
2
( m - bpm)]
4+
bound an
oligonucleotide containing a single adenine bulge signifi cantly more strongly than
the corresponding control, nonbulged, oligonucleotide.
98
Furthermore, NOESY
experiments indicated that the ruthenium complex bound specifi cally at the bulge
site in the self-complementary tridecanucleotide d(CCG
A
GAATTCCGG)
2
(where
the A in bold represents the adenine bulge). Simple binding models, consistent with
Figure 11.5
A structural representation of the adenine bulge (A
4
) containing
tridecanucleotide
