Chemistry Reference
In-Depth Information
Figure 7.7
Chemical formulae of selected platinum-organic G-quadruplex ligands known to
stabilize specifi cally G-quadruplexes over duplex DNA. Platinum complexes (A) are unable
to platinate G-quadruplexes once bound to it, whereas platinum complexes (B) are potentially
able to platinate G-quadruplexes since they are monofunctional. However, this possibility has
not been yet investigated
structure of (T
4
G
4
T
4
)
4
showed p-stacking interaction of the aromatic system
with the guanines of both external G-quartets. Surprisingly, the Pt(II) is off-
centre due to the presence of three hydrogen bonds between the ethylene-
diamine ligand and the DNA phosphate backbone.
122
(ii) A mono-substituted phenanthroline has been synthesized and used as a triden-
date
N,N,N
-ligand to coordinate to Pt(II)
123
(Figure 7.7B). This design was
based on molecular modelling suggesting that the Pt(II) ion could be positioned
over the cation channel at the centre of an accessible G-quartet, optimizing the
stacking interactions. In the same context, three Pt(II)-terpyridine complexes
have been synthesized (Figure 7.7B).
108
The monosubstituted phenanthroline-
Pt(II) complex induces a high degree of stabilization for quadruplexes (increase
in the melting temperature over 20 °C) and is selective for quadruplex structure
over duplex by a factor of 40. A comparable increase in melting temperature
(11 - 16 ° C) was observed with the Pt(II) - terpyridine complexes. Moreover, the
metal-free ligand has considerably lower effect on the stabilization than Pt(II)
complexes, suggesting that the presence of a Pt(II) centre plays an important
role in quadruplex stabilization. Since both platinum complexes are monofunc-
tional, (one Cl
−
labile ligand), they should be able to link covalently to purines
of G-quadruplexes. However, this possibility has not yet been investigated by
the authors.
Studies from our group pointed out that G-quadruplex structures, against all
expectations, were potential targets for Pt(II) coordination.
78,124 - 127
). We fi rst ana-
lysed the possible platination of two quadruplex structures of the
Tetrahymena
