Chemistry Reference
In-Depth Information
in a Hoogsteen pairing geometry. The presence of cations is required for G-quartet
formation. Cations reduce repulsions amongst guanine carbonyl oxygen atoms and
contribute to enhanced base-base stacking interactions.
5 - 8,10,84 - 88
The coordination of
cations by the closely spaced carbonyl oxygen atoms of a G-quartet was postulated
long before the fi rst high-resolution structure of a G-quadruplex was determined.
It is noteworthy that G-quartets interact with dehydrated cations via inner sphere
coordination.
89
It is therefore not surprising that formation, stability and structural
details of G-quadruplexes are dependent on cation species and cation
concentration.
3.1.1 Stoichiometry
DNA G-quadruplexes can be formed with different numbers of oligonucleotide
strands (i.e. 1, 2 or 4, Figure 3.2). In a tetramolecular structure four strands associate
to form a G-quadruplex. Such quadruplexes are usually comprised of four strands
in a parallel orientation (Figure 3.2a). Parallel quadruplexes have all guanine resi-
dues in an
anti
conformation. Association of two oligonucleotides with two G-tracts,
which can be different, leads to a bimolecular structure with a so-called fold-back
topology (Figure 3.2b). As a result, some of the G residues adopt the
syn
conforma-
tion and strands adopt different alternations of parallel and antiparallel orientations.
The topological model in Figure 3.2b shows a G-quadruplex with two parallel and
two antiparallel strands. In this structure each strand has one parallel and one
antiparallel neighbour. An example of such an arrangement has been established
experimentally by the structure of d[(G
4
T
4
G
4
)
2
] (see below). A monomolecular G-
quadruplex can be adopted by sequences consisting of four G-tracts, separated by
Figure 3.2
(Plate 1)
Variation in strand stoichiometry and topology of inter- and intramo-
lecular G-quadruplex structures: (a) tetramolecular structure with all four parallel strands and
all
anti
glycosidic torsion angles; (b) bimolecular and (c) monomolecular structures with
antiparallel strands and alternating
syn
(in orange) and
anti
(in blue) orientations across gly-
cosidic bonds (See colour plate section)
