Triplex‐Forming Peptide Nucleic Acids with Extended Backbones

• DOI: 10.1002/cbic.202000432
• Publication Date: 2020-07-22T19:45:05Z
• Authors: Vipin Kumar; Nikita Brodyagin; Eriks Rozners
• Keywords: Peptide nucleic acid; Isothermal Titration Calorimetry

Abstract Peptide nucleic acid (PNA) forms a triple helix with double‐stranded RNA (dsRNA) stabilized by hydrogen‐bonding zipper formed PNA's backbone amides (N−H) interacting phosphate oxygens. This pattern is enabled the matching ∼5.7 Å spacing (typical for A‐form dsRNA) between and We hypothesized that extending one −CH 2 − group might bring distance PNA amide groups closer to 7 Å, which favourable hydrogen bonding B‐form dsDNA Extension of was expected selectively stabilize PNA‐DNA triplexes compared PNA‐RNA. To test this hypothesis, we synthesized triplex‐forming PNAs had pseudopeptide backbones extended an additional in three different positions. Isothermal titration calorimetry measurements binding affinity these analogues matched dsRNA showed that, contrary our structural reasoning, at any position strong negative effect on triplex stability. Our results suggest have inherent preference A‐form‐like conformations when acids. It appears original six‐atom‐long almost perfect fit