Mutually exclusive inhibition of herpesvirus DNA polymerase by aphidicolin, phosphonoformate, and acyclic nucleoside triphosphates.
Dual inhibitor studies were performed to examine the interaction of aphidicolin, phosphonoformate, 9-(2-hydroxyethoxymethyl)guanine triphosphate, and 9-(1,3-dihydroxy-2-propoxymethyl)guanine triphosphate with herpes simplex virus DNA polymerase. Kinetic data indicated that inhibition by one agent prevents simultaneous inhibition by a second agent, producing a mutually exclusive inhibition pattern. This suggested that binding sites on the DNA polymerase molecule for these compounds are kinetically overlapping. These findings should be taken into consideration for the design of future antiviral compounds and combination chemotherapy protocols.
Frank
K B
KB
Cheng
Y C
YC
D000212:Acyclovir / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D016590:Aphidicolin; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors; D004224:Diterpenes / Q000494:pharmacology*; D017245:Foscarnet; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D019384:Nucleic Acid Synthesis Inhibitors; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D018139:Simplexvirus / Q000201:enzymology*
C040342:9-(1,3-dihydroxy-2-propoxymethyl)guanine triphosphate; D000998:Antiviral Agents; D004224:Diterpenes; D019384:Nucleic Acid Synthesis Inhibitors; D009943:Organophosphorus Compounds; D017245:Foscarnet; D016590:Aphidicolin; D006160:Guanosine Triphosphate; D003851:Deoxyribonucleases; D010746:Phosphonoacetic Acid; D000212:Acyclovir