Combining G-quadruplex targeting motifs on a single PNA scaffold: A hybrid (3+1) PNA-DNA bimolecular quadruplex

نویسندگان

  • Alexis Paul
  • Poulami Sengupta
  • Yamuna Krishnan
  • Sylvain Ladame
چکیده

We describe the first Gquadruplex targeting approach that combines an intercalation and a hybridization strategy by investigating the interaction of a G-rich PNA acridone conjugate 1 with a three repeat fragment of the human telomere G3 to form a hybrid PNA-DNA quadruplex mimicking the biologically relevant (3+1) pure DNA dimeric telomeric quadruplex. Using a combination of UV, CD and fluorescence spectroscopy as well as mass spectrometry, we show that PNA 1 can induce the formation of a bimolecular hybrid quadruplex even at low salt concentration upon interaction with a single-stranded three repeat fragment of telomeric DNA. However PNA 1 cannot invade a short fragment of B-DNA even if the latter contains a CCC motif complementary to the PNA sequence. These studies could open up new possibilities for the design of a novel generation of quadruplex ligands that target not only the external features of the quadruplex but also its central core constituted by the tetrads themselves.

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تاریخ انتشار 2015