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5'
T14
5'
T14
T13
T13
G3
G15
G15
G3
G12
G4
G12
3'
G21
G16
G24
G16
G11
G4
G5
G11
G17
G22
G23
G17
G5
T20
G10
G6
G10
G6
T19
G9
G9
G23
G22
T7
T7
G18
T8
G18
T8
G24
T19
3'
G21
T20
B
A
Figure 7.8
Schematic structures of the G-quadruplex formed by the telomeric sequence of
Tetrahymena
. The antiparallel structure (A) has been solved by chemical probes
128
and the
mixed-hybrid one (B) has been solved by NMR
130
sequence, (T
2
G
4
)
4
, which have been structurally determined by Williamson
et al.
128
,
Henderson
et al
.
129
and Wang and Patel.
130
These structures contain four guanines
in their loops in addition of the three G-quartets (Figure 7.8). The four guanines of
a G-quartet have their N7 atom involved in hydrogen bonding. Therefore, within a
G-quadruplex structure, we postulated that only the four guanines not included in
the G-quartets should react with Pt(II) complexes. The two quadruplex structures
exhibit various loop and strand orientations (Figure 7.8), in which different guanines,
not included in the G-quartets, are exposed: G3, G9, G15, G21 in the antiparallel
structure (Figure 7.8A) and G6, G9, G15, G24 in the hybride structure (Figure 7.8B).
Using the monofunctional triammine complex [Pt(II)(NH
3
)
3
(H
2
O)]
2+
, we have
shown that only the four guanines G3, G9 G15 and G21, (but not G6 and G24) are
platinated, suggesting the existence of the antiparallel structure as the major one in
solution. However, the four guanines were not equally accessible for platination.
Molecular dynamics simulations were used in order to interpret these results and
allowed us to conclude that the relative accessibility of the N7 atom of the free
guanines depends on their stacking with the neighbouring bases and on their binding
with the central cation, positioned within the loops.
124
Therefore [Pt(II)(NH
3
)
3
(H
2
O)]
2+
could be considered as a useful tool to check the accessibility of the nucleophilic
sites of purines. Furthermore, the difunctional Pt(II) complexes,
cis
- and
trans
-
[Pt(II)(NH
3
)
2
(H
2
O)
2
]
2+
, were shown to crosslink both ends of the quadruplex struc-
ture of (T
2
G
4
)
4
, since G3-G15 and G9-G21 crosslinks were formed. Molecular
dynamics simulations indicated that these crosslinks occurred without perturbing
the overall structure and the quartet stacking.
124
