Effect of oxetanocin G, a novel nucleoside analog, on DNA synthesis by hepatitis B virus virions.
The novel nucleoside oxetanocin G, 9-(2-deoxy-2-hydroxymethyl-beta-D-erythro-oxetanosyl)guanine (OXT-G), that is a derivative of oxetanocin A, was studied in relation to its action on the synthesis of hepatitis B virus (HBV) DNA and cellular DNA in an HBV-producing cell line, HB611 (T. Tsurimoto, A. Fujiyama, and K. Matsubara, Proc. Natl. Acad. Sci. USA 84:444-448, 1987). The median effective concentration of OXT-G against HBV replication was 1.5 microM, and the median cytotoxic concentration was more than 1,000 microM. At the same concentration, OXT-G did not inhibit cellular DNA synthesis or viral RNA synthesis. Chemically synthesized OXT-GTP inhibited the HBV endogenous DNA polymerase reaction and was incorporated into HBV DNA strands at a low efficiency compared with the incorporation of dGTP. A synthetic primer-template study revealed that OXT-GTP was incorporated into DNA strands at a low efficiency and that further extension of the DNA strand by using the 2' position of the incorporated OXT-G could take place.
Nagahata
T
T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kitagawa
M
M
Matsubara
K
K
D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D054303:HIV Reverse Transcriptase; D006515:Hepatitis B virus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D019384:Nucleic Acid Synthesis Inhibitors; D012367:RNA, Viral / Q000096:biosynthesis; D018894:Reverse Transcriptase Inhibitors; D013936:Thymidine / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D019384:Nucleic Acid Synthesis Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C057479:oxetanocin G; D006147:Guanine; D054303:HIV Reverse Transcriptase; D004259:DNA-Directed DNA Polymerase; D013936:Thymidine