Chemistry Reference
In-Depth Information
conversion of d[(G
3
T
4
G
3
)
2
] from its Na
+
form to K
+
form is associated with a net
free energy change (D
D
G
0
) of 1.7 kcal mol
− 1
.
168
3.2.1 Molecular Switches
In addition to their central role in stabilizing G-quadruplexes, cations also play an
important role in determining G-quadruplex structure. A systematic study of G-rich
oligonucleotides containing runs of G residues of various lengths and with varying
numbers of intervening residues, revealed a cation-dependent pattern for the G-
quadruplex folds.
48,75,105,107,109,110,113,122,177 - 179
The possibility of cation-induced changes
in G-quadruplex structures has formed the basis of the hypothesis that DNA G-
quadruplexes might function as molecular switches.
180,181
The interconversion of G-
rich DNA sequences between antiparallel and parallel G-quadruplexes could be
controlled by Na
+
/K
+
concentrations.
182 - 186
Thomas and coworkers used Raman spec-
troscopy to generate a phase diagram of antiparallel and parallel G-quadruplex
structures, as controlled by concentrations of Na
+
and K
+
ions.
180
At low cation con-
centrations d[(T
4
G
4
)
4
] folds into an antiparallel diagonal-loop G-quadruplex. Higher
cation concentrations and K
+
ions lead to the formation of parallel structures.
180
An
entirely different ion-dependent conformational switch has been observed for
d(G
2
AG
2
AG). At a moderate ionic strength of 150 mM NaCl, this oligonucleotide
forms a four-stranded quadruplex.
103
The bimolecular quadruplex comprises a
unique A • (G • G • G • G) • A hexad motif that is stabilized by sheared GA base pairs,
in addition to the G-quartet.
103
At low ionic strength d(G
2
AG
2
AG) forms a two-
stranded V - shaped ' arrowhead ' motif.
187
The cation binding sites associated with
the two folds of this oligonucleotide suggest a rational for the cation-dependent
switch.
A cation-dependent loop polymorphism has been observed in the bimolecular
G - quadruplex adopted by d(G
3
CT
4
G
3
C) that contains G • C • G • C quartets, along
with G - quartets.
94,188
The conformation of thymines in the edge-wise loops is differ-
ent between Na
+
and K
+
forms. The loop conformation is affected by the presence
of a K
+
binding site in the T
4
loop, whereas there is no such binding site for Na
+
ions. The loop conformation, in turn, is sensitive to the conformation of the outer
G-quartet, which is substantially different in the two cation forms. A K
+
ion is
postulated to penetrate the G•C•G•C quartet at the expense of hydrogen bonding
between the G-C base pairs.
94,188
Some of the aspects of cation coordination within G-quadruplexes and
their consequences that are mentioned and introduced in a rather general and
limited way in the section above are further discussed in greater detail with specifi c
examples in the rest of this contribution.
3.3 Structure of Sequences Consisting of Human Telomere Repeats
Human telomeric DNA ends are composed of tandem TTAGGG repeats. It has
been known for over a decade that G-quadruplexes formed from human telomeric
