Acyclic guanosine analogs as substrates for varicella-zoster virus thymidine kinase.
This study was performed to obtain information on the enzymatic background to the antiviral activity of acyclic guanosine analogs. Five acyclic guanosine analogs, the (R)- and (S)-enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine, 9-[(2-hydroxyethoxy)methyl]guanine, and 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine, were compared in enzyme kinetic experiments using purified varicella-zoster virus and human placenta mitochondrial thymidine kinase (TK). All analogs showed competitive patterns of inhibition in the phosphorylation of thymidine by varicella-zoster virus TK, but only low affinities and phosphorylation rates were observed. No affinity for the mitochondrial TK was observed for any of the analogs.
D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014645:Herpesvirus 3, Human / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D010766:Phosphorylation; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects
D006151:Guanosine; D013937:Thymidine Kinase