Two separate structural elements of a G-quadruplex (G4), a vacant site and a flanking single-strand, provide an opportunity for specific targeting of a particular G4 structure via dual recognition. Here, we show that a short peptide nucleic acid (PNA) can specifically recognize and bind to a G4 at sub-micromolar affinity based on both G-tetrad vacant site filling and complementary duplex formation. This sequence-guided guanine-anchoring strategy can be further developed for specific targeting of G4 structures using short DNA, LNA and PNA strands.
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