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

Peptide nucleic acids (PNAs) are linear equivalents of DNA with a neutral acyclic polyamide backbone that has nucleobases attached via -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(/)--PNA] is designed to have a second nucleobase attached via amide spacer to a side chain at Cγ on the repeating units of PNA oligomer. Cγ-bimodal PNA oligomers that have two nucleobases per unit are demonstrated to concurrently bind two different complementary DNAs, to form duplexes from both -amide side and Cγ side. In such PNA:DNA ternary complexes, the two duplexes share a common PNA backbone. The ternary DNA 1:Cγ(/)--PNA:DNA 2 complexes exhibit better thermal stability than the isolated duplexes, and the Cγ()--PNA duplexes are more stable than Cγ()--PNA duplexes. Bimodal PNAs are first examples of PNA analogues 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.