Physicochemical and biochemical properties of 2',5'-linked RNA and 2',5'-RNA:3',5'-RNA "hybrid" duplexes

Biochemistry. 1998 May 19;37(20):7478-86. doi: 10.1021/bi980160b.


In recent publications, oligonucleotides joined by 2',5'-linkages were found to bind to complementary single-stranded RNA but to bind weakly, or not at all, to single-stranded DNA [e.g., P. A. Giannaris and M. J. Damha (1993) Nucleic Acids Res. 21, 4742-4749]. In this work, the biochemical and physicochemical properties of 2',5'-linked oligoribonucleotides containing mixed sequences of the four nucleobases (A, G, C, and U) were evaluated. CD spectra of RNA:2', 5'-RNA duplexes were compared with the spectra of DNA:DNA, RNA:RNA, and DNA:RNA duplexes of the same base sequence. The CD results indicated that the RNA:2',5'-RNA duplex structure more closely resembles the structure of the RNA:DNA hybrid, being more A-form than B-form in character. The melting temperature (Tm) values of the backbone-modified duplexes were compared with the Tm values of the unmodified duplexes. The order of thermal stability was RNA:RNA > DNA:DNA approximately RNA:DNA approximately DNA:RNA > RNA:2',5'-RNA > 2',5'-RNA:2',5'-RNA >> DNA:2',5'-RNA (undetected). RNA:2',5'-RNA duplexes are not substrates of the enzyme RNase H (Escherichia coli, or HIV-1 reverse transcriptase), but they can inhibit the RNase H-mediated cleavage of a natural DNA:RNA substrate. Structural models that are consistent with the selective association properties of 2',5'-linked oligonucleotides are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Conformation
  • Chemical Phenomena
  • Chemistry, Physical
  • Circular Dichroism
  • DNA / chemistry
  • Enzyme Induction / drug effects
  • Hot Temperature
  • Nucleic Acid Conformation
  • Nucleic Acid Heteroduplexes / chemical synthesis
  • Nucleic Acid Heteroduplexes / chemistry*
  • Nucleic Acid Heteroduplexes / pharmacology
  • Oligoribonucleotides / chemical synthesis
  • Oligoribonucleotides / chemistry*
  • Oligoribonucleotides / pharmacology
  • RNA / chemical synthesis
  • RNA / chemistry*
  • RNA / pharmacology
  • Ribonuclease H / biosynthesis
  • Ribonuclease H / metabolism
  • Spectrophotometry, Ultraviolet
  • Substrate Specificity / drug effects
  • Substrate Specificity / genetics


  • Nucleic Acid Heteroduplexes
  • Oligoribonucleotides
  • RNA
  • DNA
  • Ribonuclease H