title: Combining G-quadruplex targeting motifs on a single peptide nucleic acid scaffold: a hybrid (3+1) PNA-DNA bimolecular quadruplex.
abstract: 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.
authors.affiliation: Institut de Science et d'Ingénierie, Supramoléculaires (ISIS), Université Louis Pasteur, CNRS UMR 7006, 8 Allée Gaspard Monge, Strasbourg Cédex, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Paul
authors.forename: Poulami
authors.initials: P
authors.lastname: Sengupta
authors.forename: Yamuna
authors.initials: Y
authors.lastname: Krishnan
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladame
mesh_terms: 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
chemical_list: D020135:Peptide Nucleic Acids; D004247:DNA