Combining G-quadruplex targeting motifs on a single peptide nucleic acid scaffold: a hybrid (3+1) PNA-DNA bimolecular quadruplex.
We describe the first G-quadruplex targeting approach that combines intercalation and hybridization strategies by investigating the interaction of a G-rich peptide nucleic acid (PNA) acridone conjugate 1 with a three-repeat fragment of the human telomere G 3 to form a hybrid PNA-DNA quadruplex that mimicks the biologically relevant (3+1) pure DNA dimeric telomeric quadruplex. Using a combination of UV and fluorescence spectroscopy, circular dichroism (CD), and 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.
Paul
Alexis
A
Institut de Science et d'Ingénierie, Supramoléculaires (ISIS), Université Louis Pasteur, CNRS UMR 7006, 8 Allée Gaspard Monge, Strasbourg Cédex, France.
Sengupta
Poulami
P
Krishnan
Yamuna
Y
Ladame
Sylvain
S
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
D020135:Peptide Nucleic Acids; D004247:DNA