Highly stable duplex formation by artificial nucleic acids acyclic threoninol nucleic acid (aTNA) and serinol nucleic acid (SNA) with acyclic scaffolds

Chemistry. 2013 Oct 11;19(42):14151-8. doi: 10.1002/chem.201301578. Epub 2013 Aug 23.


The stabilities of duplexes formed by strands of novel artificial nucleic acids composed of acyclic threoninol nucleic acid (aTNA) and serinol nucleic acid (SNA) building blocks were compared with duplexes formed by the acyclic glycol nucleic acid (GNA), peptide nucleic acid (PNA), and native DNA and RNA. All acyclic nucleic acid homoduplexes examined in this study had significantly higher thermal stability than DNA and RNA duplexes. Melting temperatures of homoduplexes were in the order of aTNA>PNA≈GNA≥SNA≫RNA>DNA. Thermodynamic analyses revealed that high stabilities of duplexes formed by aTNA and SNA were due to large enthalpy changes upon formation of duplexes compared with DNA and RNA duplexes. The higher stability of the aTNA homoduplex than the SNA duplex was attributed to the less flexible backbone due to the methyl group of D-threoninol on aTNA, which induced clockwise winding. Unlike aTNA, the more flexible SNA was able to cross-hybridize with RNA and DNA. Similarly, the SNA/PNA heteroduplex was more stable than the aTNA/PNA duplex. A 15-mer SNA/RNA was more stable than an RNA/DNA duplex of the same sequence.

Keywords: DNA; helical structures; melting temperature; nucleic acids; thermodynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Alcohols / chemistry*
  • Base Sequence
  • Butylene Glycols / chemistry*
  • Circular Dichroism
  • DNA / chemistry*
  • Models, Molecular
  • Nucleic Acid Conformation
  • Nucleic Acids / chemistry*
  • Propanolamines / chemistry*
  • Propylene Glycols / chemistry*
  • RNA / chemistry*
  • Temperature
  • Thermodynamics


  • Amino Alcohols
  • Butylene Glycols
  • Nucleic Acids
  • Propanolamines
  • Propylene Glycols
  • threoninol
  • RNA
  • DNA
  • serinol