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Multivalent LK?-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)K?-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 ?-modification and addition of a peptide ligand does not disrupt the heteroquadruplex. Although the unmodified PNA1 forms a quadruplex with itself, the ?-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.

SUBMITTER: Gupta P

PROVIDER: S-EPMC5603266 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Multivalent LKγ-PNA oligomers bind to a human telomere DNA G-rich sequence to form quadruplexes.

Gupta Pankaj P Rastede Elizabeth E EE Appella Daniel H DH

Bioorganic & medicinal chemistry letters 20150729 21

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- ...[more]

PMID: 26259805

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