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Molecular Assembly of Triplex of Duplexes from Homothyminyl-Homocytosinyl Cγ(S/R)-Bimodal Peptide Nucleic Acids with dA₈/dG₆ and the Cell Permeability of Bimodal Peptide Nucleic Acids.

ABSTRACT: Peptide nucleic acids (PNAs) are analogues of DNA with a neutral acyclic polyamide backbone containing nucleobases attached through a t-amide link on repeating units of aminoethylglycine (aeg). They bind to complementary DNA or RNA in a sequence-specific manner to form duplexes with higher stablity than DNA:DNA and DNA:RNA hybrids. We have recently explored a new type of PNA termed bimodal PNA (bm-PNA) designed with two nucleobases per aeg repeating unit of PNA oligomer and attached at Cα or Cγ of each aeg unit through a spacer sidechain. We demonstrated that Cγ-bimodal PNA oligomers with mixed nucleobase sequences bind concurrently two different complementary DNAs, forming double duplexes, one from each t-amide and Cγ face, sharing a common PNA backbone. In such bm-PNA:DNA ternary complexes, the two duplexes show higher thermal stability than individual duplexes. Herein, we show that Cγ(S/R)-bimodal PNAs with homothymines (T₈) on a t-amide face and homocytosine (C₆) on a Cγ-face form a conjoined pentameric complex consisting of a triplex (bm-PNA-T₈)₂:dA₈ and two duplexes of bm-PNA-C₆:dG₆. The pentameric complex [dG₆:Cγ(S/R)-bm-PNA:dA₈:Cγ(S/R)-bm-PNA:dG₆] exhibits higher thermal stability than the individual triplex and duplex, with Cγ(S)-bm-PNA complexes being more stable than Cγ(R)-bm-PNA complexes. The conjoined duplexes of Cγ-bimodal PNAs can be used to generate novel higher-order assemblies with DNA and RNA. The Cγ(S/R)-bimodal PNAs are shown to enter MCF7 and NIH 3T3 cells and exhibit low toxicity to cells.

SUBMITTER: Bhingardeve P

PROVIDER: S-EPMC8340421 | biostudies-literature |

REPOSITORIES: biostudies-literature

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