Synthesis and hybridization properties of l-oligodeoxynucleotide analogues fixed in a low anti glycosyl conformation

Org Biomol Chem. 2004 Jan 21;2(2):183-9. doi: 10.1039/b312276j. Epub 2003 Dec 10.

Abstract

We have synthesized l-type enantiomers (cU and cA) of nucleoside analogues, whose glycosyl bonds are fixed in a low anti conformation (ap glycosyl conformation, [small chi][approximate] 180[degree]), and incorporated them into oligonucleotides to evaluate the hybridization ability with natural DNA and RNA sequences. Although the incorporation of the modified nucleosides into oligonucleotides decreased the hybridization ability with unmodified complementary DNA sequences, the fully-substituted 12mers (cU(12) and cA(12)) still retained the hybridization ability with the complementary unmodified DNA 12mers, regardless of their unnatural l-chirality. In contrast, cU(12) and cA(12) showed different hybridization behavior with complementary unmodified RNA 12mers. cU(12) forms a more stable duplex with rA(12) than the corresponding natural 12mer (dT(12)), whereas cA(12) cannot hybridize with rU(12). Based on the model structure of cU(12)-rA(12), we discuss these experimental results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carbohydrate Conformation
  • Circular Dichroism
  • DNA / chemistry*
  • Drug Stability
  • Glycosides / chemical synthesis
  • Glycosides / chemistry
  • Glycosides / metabolism
  • Models, Molecular
  • Nucleic Acid Conformation
  • Nucleic Acid Denaturation
  • Nucleic Acid Hybridization
  • Nucleosides / chemistry
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry*
  • Oligonucleotides / metabolism
  • Phosphoric Diester Hydrolases / metabolism
  • RNA / chemistry*
  • Snake Venoms
  • Sodium Chloride / chemistry
  • Stereoisomerism
  • Temperature

Substances

  • Glycosides
  • Nucleosides
  • Oligonucleotides
  • Snake Venoms
  • Sodium Chloride
  • RNA
  • DNA
  • Phosphoric Diester Hydrolases