double-stranded DNA PCR product being undetectable. As
shown in Fig. 3(a), the PCR product was inhibited in a
concentration-dependent manner by compound 1. The IC50
value, which indicates the concentration of compound 1
required to achieve 50% inhibition of the reaction, was found
to be 1.8 mM. To discriminate inhibitory effects from different
sources, a parallel experiment using a mutated oligomer
21 Gmu (50-GGGTTAGAATTAGGGTTAGGG-30) which
could not form G-quadruplex was performed. In that case,
no inhibition was observed even at the highest concentration
of 25 mM (see Fig. 3(b)). Compound 2 was also tested in this
assay, and not surprisingly, it showed weak inhibition ability
(Fig. S3, see ESIw). The IC50 was about 100 mM.
All the above results have shown compound 1 is a good
G-quadruplex inducing and stabilizing ligand, while 2 is not.
We suggested the tremendous difference between the two
compounds was due to the structural difference of the cores.
Most recently bis-indole carboxamides linked with a pyridine
ring have been studied for G-quadruplex recognition.25 The
H-bonds between NH of the pyridine ring and benzimidazole
may play an important role in the planar structure, and a
planar central core may be vital for the binding of this kind of
ligand with the G-quadruplex. UV-Vis titration was used to
evaluate the binding mode of compound 1 with the G-quad-
ruplex. Compound 1 demonstrated 9 nm red shifts and
significant hypochromicity of 42% (Fig. S4, see ESIw). We
assumed the benzimidazole group may be ideally suited for
p–p stacking interactions with guanine, considering their
structural similarity, and compound 1 could be bound to the
ends of the G-quadruplex through p–p stacking.26
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In summary, two new bis(benzimidazole)aryl derivatives have
been synthesized and evaluated as a new class of G-quadruplex
inducing and stabilizing ligands. All the experimental results have
shown that the bis(benzimidazole)pyridine derivative 1 can
induce and stabilize the formation of a G-quadruplex. SPR
sensorgrams showed the strong binding and obvious selectivity
of compound 1 for G-quadruplex DNA vs. ds DNA. The
difference of activities between 1 and 2 convinced us that, for
this kind of compounds, the planar conformation of cores is vital
for their binding with G-quadruplex.
This work was partially supported by the National Science
of Foundation of China (No. 20672084, 20621502), National
Science Fund for Distinguished Young Scholars (No.
20425206), the Cultivation Fund of the Key Scientific and
Technical Innovation Project, the Ministry of Education of
China (No. 706040).
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This journal is The Royal Society of Chemistry 2008
4566 | Chem. Commun., 2008, 4564–4566