Solution structure of an arabinonucleic acid (ANA)/RNA duplex in a chimeric hairpin: comparison with 2'-fluoro-ANA/RNA and DNA/RNA hybrids

Nucleic Acids Res. 2001 Nov 1;29(21):4284-93. doi: 10.1093/nar/29.21.4284.


Hybrids of RNA and arabinonucleic acid (ANA) as well as the 2'-fluoro-ANA analog (2'F-ANA) were recently shown to be substrates of the enzyme RNase H. Although RNase H binds to double-stranded RNA, no cleavage occurs with such duplexes. Therefore, knowledge of the structure of ANA/RNA hybrids may prove helpful in the design of future antisense oligonucleotide analogs. In this study, we have determined the NMR solution structures of ANA/RNA and DNA/RNA hairpin duplexes and compared them to the recently published structure of a 2'F-ANA/RNA hairpin duplex. We demonstrate here that the sugars of RNA nucleotides of the ANA/RNA hairpin stem adopt the C3'-endo (north, A-form) conformation, whereas those of the ANA strand adopt a 'rigid' O4'-endo (east) sugar pucker. The DNA strand of the DNA/RNA hairpin stem is flexible, but the average DNA/RNA hairpin structural parameters are close to the ANA/RNA and 2'F-ANA/RNA hairpin parameters. The minor groove width of ANA/RNA, 2'F-ANA/RNA and DNA/RNA helices is 9.0 +/- 0.5 A, a value that is intermediate between that of A- and B-form duplexes. These results rationalize the ability of ANA/RNA and 2'F-ANA/RNA hybrids to elicit RNase H activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabinonucleotides / chemistry
  • Arabinonucleotides / metabolism*
  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular*
  • Nucleic Acid Conformation*
  • Nucleic Acid Heteroduplexes / chemistry*
  • Nucleic Acid Heteroduplexes / genetics
  • Nucleic Acid Heteroduplexes / metabolism
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Pliability
  • RNA / chemistry*
  • RNA / genetics
  • RNA / metabolism
  • RNA Stability
  • Ribonuclease H / metabolism
  • Ribose / chemistry
  • Ribose / metabolism
  • Solutions
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thermodynamics


  • Arabinonucleotides
  • Nucleic Acid Heteroduplexes
  • Oligonucleotides
  • Solutions
  • RNA
  • Ribose
  • DNA
  • Ribonuclease H