Synthesis and structural analysis of oxadiazole carboxamide deoxyribonucleoside analogs

Nucleosides Nucleotides Nucleic Acids. 2005;24(10-12):1919-45. doi: 10.1080/15257770500269267.


Two novel C-linked oxadiazole carboxamide nucleosides 5-(2'-deoxy-3',5'-beta-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-5-carboxamide (1) and 5-(2'-deoxy-3',5'-beta-D-erythro-pentofuranosyl)-1,2,4-oxadiazole-3-carboxamide (2) were successfully synthesized and characterized by X-ray crystallography. The crystallographic analysis shows that both unnatural nucleoside analogs 1 and 2 adapt the C2'-endo ("south") conformation. The orientation of the oxadiazole carboxamide nucleobase moiety was determined as anti (conformer A) and high anti (conformer B) in the case of the nucleoside analog 1 whereas the syn conformation is adapted by the unnatural nucleoside 2. Furthermore, nucleoside analogs 1 and 2 were converted with high efficiency to corresponding nucleoside triphosphates through the combination chemo-enzymatic approach. Oxadiazole carboxamide deoxyribonucleoside analogs represent valuable tools to study DNA polymerase recognition, fidelity of nucleotide incorporation, and extension.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Crystallography, X-Ray
  • DNA-Directed DNA Polymerase / chemistry
  • Deoxyribonucleosides / chemical synthesis*
  • Deoxyribonucleosides / chemistry
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry
  • Stereoisomerism


  • Deoxyribonucleosides
  • Oxadiazoles
  • DNA-Directed DNA Polymerase