Chemistry Reference
In-Depth Information
three regions that can be any combination of residues, including G. An example of
such an intramolecular structure with antiparallel strands and alternating
syn
and
anti
orientations across the glycosidic bonds is shown in Figure 3.2c. Quadruplexes
are labelled as antiparallel when at least one of the four strands is antiparallel to
the others. This type of topology is found in the majority of bimolecular and in many
monomolecular G-quadruplex structures. Antiparallel folds exhibit both
syn
and
anti
guanine residues within individual G-quartets, which are arranged in a way that
is in accordance with strand orientations.
Recently, a formalism was proposed describing the interdependency of a set
of structural descriptors as a geometric basis for folding of monomolecular G-
quadruplex topologies.
90
The formalism is a fundamental step towards the prediction
of monomolecular G-quadruplex folding topologies from primary structures. In
addition to establishing rules that will enable the prediction of folding topologies,
the work of Webba da Silva
90
suggested that there could be other folding topologies
in addition to those that have been identifi ed experimentally so far.
3.1.2 Loops
G-quadruplex structures may also be classifi ed according to the location of the loops
that link the neighbouring G-tracts involved in G-quartets. The location and length
of the loops in combination and in addition to the number of stacked G-quartets
and the number and the pattern of the strand directionalities all contribute to a
plurality of G-quadruplex structures. Edge-wise (or lateral) loops join adjacent G-
strands by spanning the edge of an outer G-quartet as shown schematically in Figure
3.3a. These loops are generally composed of two or more residues.
91,92
This type of
loop structure has been observed in two NMR solution-state structures of asym-
metric G-quadruplexes of the d(TG
4
T
2
G
4
T) sequence
93
and in the bimolecular G-
quadruplex structure formed by the sequence d(G
3
CT
4
G
3
C).
94
Two of the edge-wise
loops can be located either on the same or on opposite sides of a G-quadruplex
core, resulting in head - to - head or head - to - tail arrangements, respectively. Two dis-
tinct bimolecular G-quadruplexes were formed by d(G
4
T
3
G
4
).
95
One of the struc-
tures exhibited a head-to-tail lateral loop dimer in which all adjacent strands were
Figure 3.3
Loop structures: (a) edge-wise loops connecting antiparallel strands on the
same side of the G-quadruplex; (b) diagonal loops connecting opposite antiparallel strands;
(c) external double-chain reversal loops connecting parallel strands
