Synthesis and structural analysis of oxadiazole carboxamide deoxyribonucleoside analogs.
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.
Adelfinskaya
Olga
O
Walther Cancer Institute, Indianapolis, Indiana, USA,.
Wu
Weidong
W
Davisson
V Jo
VJ
Davisson
V J
VJ
Bergstrom
Donald E
DE
D018360:Crystallography, X-Ray; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry; D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D003853:Deoxyribonucleosides; D010069:Oxadiazoles; D004259:DNA-Directed DNA Polymerase