Abstract:
Guanine rich nucleotide sequences of specific pattern are capable of forming unusual
secondary structures called G-quadruplexes (G4s). In silico studies have shown that
putative G-quadruplex forming motifs (pG4s) are frequently present in functionally
important regions of the genome. But formation of G-quadruplex structures by these
pG4s in cells remains elusive. In this study, we made an attempt to isolate intrinsic Gquadruplex
structure from human cells using biotinylated quadruplex interacting small
organic molecules. The ligands showed significant affinity towards structurally different
G4s in vitro. This interaction was observed to be selective towards G4s over duplex
DNA. Biotinylated ligands were then used to perform Chromatin immuno-precipitation
from human cells to isolate cellular G-quadruplex structures. Even though the ligands
showed selective binding to G-quadruplex structures in vitro, the methodology used in
this study failed to pull down G4s selectively from cells. This demands the need of
alternative approaches to identify cellular G-quadruplexes. The ligands have shown
significant inhibition of growth and proliferation of cancer cells. This implicates their
potential applications in cancer therapeutics.
