Metabolism of 9-(1,3-dihydroxy-2-propoxymethyl)guanine, a new anti-herpes virus compound, in herpes simplex virus-infected cells.
The metabolism of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), one of the most promising new anti-herpes virus compounds, in HeLa cells infected with herpes simplex virus type 1 was compared with that in the uninfected HeLa cells. In the virus-infected cells, the uptake of DHPG was enhanced and the major metabolites were found to be the mono-, di-, and triphosphate derivatives. The formation of these metabolites was dependent on the extracellular concentration of DHPG (0.5 to 5.0 microM). Virus-induced thymidine kinase was capable of phosphorylating DHPG to its monophosphate which could be further phosphorylated to the di- and triphosphate derivatives by the host cellular enzymes. Incorporation of the DHPG into DNA was observed in virus-infected cells. In contrast with 9-(2-hydroxyethoxymethyl)guanine, DHPG seemed not to serve as a chain terminator, but to be incorporated internally into DNA strands.
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism*; D001692:Biological Transport; D002472:Cell Transformation, Viral; D002851:Chromatography, High Pressure Liquid; D015774:Ganciclovir; D006367:HeLa Cells / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D007700:Kinetics; D018139:Simplexvirus / Q000378:metabolism*; D014316:Tritium
D000998:Antiviral Agents; D014316:Tritium; D015774:Ganciclovir; D000212:Acyclovir