Multivalent (L)Kγ-PNA oligomers bind to a human telomere DNA G-rich sequence to form quadruplexes.

We report G-quadruplex formation between peptide nucleic acids (PNAs) composed of LKγ-PNA-G monomers and a known portion of human telomeric DNA that adopts three G3 tracts via intramolecular hydrogen bonding. The resulting complex is a bimolecular PNA–DNA heteroquadruplex. In this Letter, we show that introduction of a γ-modification and addition of a peptide ligand does not disrupt the heteroquadruplex. Although the unmodified PNA1 forms a quadruplex with itself, the γ-substituted PNAs (PNA2–PNA6) do not form G-quadruplexes on their own, at even high concentrations. The selectivity of these PNAs could influence the design of new quadruplex-targeting molecules or allow the quadruplex structure to be used as a scaffold for multivalent display of protein binding ligands.