Cγ(S/R)-Bimodal Peptide Nucleic Acids (Cγ-bm-PNA) Form Coupled Double Duplexes by Synchronous Binding to Two Complementary DNA Strands

Abstract

Peptide nucleic acids (PNA) are linear equivalents of DNA with a neutral acyclic polyamide backbone that has nucleobases attached via t-amide link on repeating units of aminoethylglycine. They bind complementary DNA or RNA with sequence specificity to form hybrids that are more stable than the corresponding DNA/RNA self duplexes. A new type of PNA termed bimodal PNA [Cγ(4S/R)- bm-PNA] is designed to have a second nucleobase attached via amide spacer to a sidechain at Cγ on the repeating aeg units of PNA oligomer. Cγ-Bimodal PNA oligomers that have two nucleobases per aeg unit is demonstrated to concurrently bind two different complementary DNAs, to form duplexes from both t-amide side and Cγ-side. In such PNA:DNA ternary complexes, the two duplexes share a common PNA backbone. The ternary DNA 1:Cγ(S/R)-bm-PNA:DNA 2 complexes exhibit better thermal stability than the isolated duplexes, and the Cγ(S)-bm-PNA duplexes are more stable than Cγ(R)-bm-PNAs duplexes. Bimodal PNAs are the first examples of PNA analogs that can form DNA2:PNA:DNA1 double duplexes via recognition through natural bases. The conjoined duplexes of Cγ-bimodal PNAs can be used to generate novel higher-level assemblies