title: Multivalent LKγ-PNA oligomers bind to a human telomere DNA G-rich sequence to form quadruplexes.
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.
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD 20892, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD 20892, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Rastede
authors.affiliation: Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD 20892, USA. Electronic address: appellad@niddk.nih.gov.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Appella
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D016615:Telomere / Q000737:chemistry*
chemical_list: D020135:Peptide Nucleic Acids; D006147:Guanine; D004247:DNA
keywords: DNA; PNA; Quadruplex