Chemistry Reference
In-Depth Information
Figure 3.4
(Plate 2)
Polymorphism of four repeats of human telomeric sequence: (a)
intramolecular G-quadruplex formed by d[AG
3
(T
2
AG
3
)
3
] as determined by NMR spectroscopy
in the presence of Na
+
ions in solution;
92
(b) the G-quadruplex fold with parallel GGG strands
and double-chain reversal loops as determined by X-ray crystallography for the same sequence
crystallized in the presence of K
+
ions;
104
(c) the topology of the four-repeat sequence in K
+
ion containing solution (so called Hybrid-1 structure);
204,205,207
(d) the fold of major form of
the unmodifi ed four-repeat sequence in K
+
ion containing solution (so called Hybrid-2 struc-
ture).
210
For clarity, only G-bases and their
syn
(in orange) and
anti
(in blue) orientations
across glycosidic bonds are shown (See colour plate section)
of Na
+
ions, was reported several years ago.
92
This monomolecular G - quadruplex is
stabilized by the three stacked G-quartets with
anti - syn - syn - anti
conformations
around individual G-quartets (Figure 3.4a). A core of the three G-quartets is held
together by strands in alternating orientations. Two of the TTA loops connect the
edges of the outer G-quartet on the same side of the structure. The third loop is a
diagonal type loop and is positioned on the other side of the G-quadruplex core.
Such loop arrangements restrict access to the outer G-quartets by potential ligands.
The 5
-ends of the oligonucleotide are found at the same end of the G-
quadruplex (Figure 3.4 a).
The crystal structure of the K
+
form shows a dramatically different fold with
all four GGG segments being parallel (Figure 3.4b).
104
All guanine residues are in
the
anti
conformation. All three TTA loops are in a double-chain reversal conforma-
tion and connect the top of one GGG strand with the bottom of the other. The loop
residues are positioned alongside the grooves rather than at the ends of the G-
quartet stack and thus give the topology a propeller shape. The double-chain reversal
′
- and 3
′
