Author:

Keywords:

DNA, PNA, Quadruplex, Base Sequence, Binding Sites, G-Quadruplexes, Guanine, Humans, Molecular Structure, Peptide Nucleic Acids, Telomere, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

We report G-quadruplex formation between peptide nucleic acids (PNAs) composed of (L)Kγ-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.