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Combining G‐Quadruplex Targeting Motifs on a Single Peptide Nucleic Acid Scaffold: A Hybrid (3+1) PNA–DNA Bimolecular Quadruplex
Author(s) -
Paul Alexis,
Sengupta Poulami,
Krishnan Yamuna,
Ladame Sylvain
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800605
Subject(s) - g quadruplex , peptide nucleic acid , chemistry , dna , circular dichroism , telomere , nucleic acid , intercalation (chemistry) , stereochemistry , biochemistry , combinatorial chemistry , inorganic chemistry
We describe the first G‐quadruplex targeting approach that combines intercalation and hybridization strategies by investigating the interaction of a G‐rich petide 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.