Chemistry Reference
In-Depth Information
movement of
15
NH
4
+
ions from the interior of the G-quadruplex to bulk solution is
faster than exchange within the G-quadruplex. Residence lifetimes of 20 and 14 s,
respectively, were established for the movement of
15
NH
4
+
ions from the two outer
binding sites into the inner binding site at 10 °C. A temperature increase to 40 °C
led to shortening of residence lifetimes to 1.5 and 2.0 s for the O
1
I and O
2
I processes,
respectively. The temperature-dependent rate constants afforded activation ener-
gies of 15.4 and 12.1 kcal mol
− 1
for O
1
I and O
2
I processes, respectively.
15
NH
4
+
ion
movement between the inside of the G-quadruplex and bulk solution is faster from
the O
2
than the O
1
binding site (Figure 3.2c, binding site O
2
is the one closer to the
two edge-wise loops). It seems that structural details of the d[G
4
(T
4
G
4
)
3
] G -
quadruplex defi ne the stiffness of individual G-quartets that intimately affect
15
NH
4
+
ion movement. The stiffness of G-quartets and steric hindrance imposed by thymine
residues in the loops contribute to the fi ve-fold difference in the exchange rate
constants through the outer G-quartets.
3.9 Summary
Our insights into the possible biological roles of G-quadruplexes and into the origins
of their topological sensitivity to cation species and concentration have benefi ted
from recent studies on structure, stability and interactions of cations with constitu-
ent G-quartets. However, it is not currently possible to delineate general rules gov-
erning the folding of G-rich DNA sequences, and more specifi cally the role of
cations in this process. Different G-rich sequences adopt distinct quadruplex topolo-
gies and, in addition, a given sequence can also fold into various different conforma-
tions, which can coexist. Human telomere sequences represent one of the best
illustrations of the structural diversity and complexity of G-quadruplex structures.
The change of metal ion species present can induce structural changes, which can
be signifi cant for some DNA sequences. A simple change in cation (salt) concentra-
tion can result in large changes in the structure and stability of a G-quadruplex.
NMR and X-ray crystallography contribute important insights into the occu-
pancy of binding sites by cations and kinetics of ion movement, which are intrinsi-
cally correlated with the structural details, dynamic fl uctuations and local fl exibility
of the DNA structure. In general, X-ray crystal structures demonstrate that cations
such as K
+
and Tl
+
are coordinated exclusively between the adjacent G-quartets
because they are too large to be coordinated within the plane of a G-quartet. In
contrast, smaller Na
+
ions can be coordinated within a G-quartet with three distinct
ligand geometries: (i) bipyrimidal coordination sites directly between two G-quartet
layers, (ii) octahedral coordination sites where the ion is coplanar with the G bases
and (iii) intermediate, less symmetric positions. Inter-Na
+
distances in the parallel-
stranded tetramolecular structure adopted by d(TG
4
T) and the bimolecular struc-
ture adopted by d(G
4
T
4
G
4
) are greater than the average distance between stacked
G-quartets. Studies on the relationship between G-quadruplex stability and cation
species have primarily considered ionic radius as the most important factor. However,
the fact that Na
+
and Ca
2+
have almost the same ionic radii illustrates that there are
