Structural Insights into Conformation Differences between DNA/TNA and RNA/TNA Chimeric Duplexes

Irina Anosova, Ewa A. Kowal, Nicholas J. Sisco, Sujay Sau, Jen Yu Liao, Saikat Bala, Eriks Rozners, Martin Egli, John C. Chaput, Wade Van Horn

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Threose nucleic acid (TNA) is an artificial genetic polymer capable of heredity and evolution, and is studied in the context of RNA chemical etiology. It has a four-carbon threose backbone in place of the five-carbon ribose of natural nucleic acids, yet forms stable antiparallel complementary Watson–Crick homoduplexes and heteroduplexes with DNA and RNA. TNA base-pairs more favorably with RNA than with DNA but the reason is unknown. Here, we employed NMR, ITC, UV, and CD to probe the structural and dynamic properties of heteroduplexes of RNA/TNA and DNA/TNA. The results indicate that TNA templates the structure of heteroduplexes, thereby forcing an A-like helical geometry. NMR measurement of kinetic and thermodynamic parameters for individual base pair opening events reveal unexpected asymmetric “breathing” fluctuations of the DNA/TNA helix. The results suggest that DNA is unable to fully adapt to the conformational constraints of the rigid TNA backbone and that nucleic acid breathing dynamics are determined from both backbone and base contributions.

Original languageEnglish (US)
Pages (from-to)1705-1708
Number of pages4
Issue number18
StatePublished - Sep 15 2016


  • DNA
  • RNA evolution
  • TNA
  • conformation analysis
  • nucleic acid dynamics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry


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