Abstract 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, ...