beta-Lapachone, an inhibitor of oncornavirus reverse transcriptase and eukaryotic DNA polymerase-alpha. Inhibitory effect, thiol dependence and specificity.
beta-Lapachone is a naturally occuring compound that can be isolated from a number of tropical trees. It is shown to be a potent inhibitor of reverse transcriptase activity from both avian myeloblastosis virus and Rauscher murine leukaemia virus. In addition, it affects eukaryotic DNA-dependent DNA polymerase-alpha activity: 50% inhibition is reached in 60-min incubation time by about 8 micron beta-lapachone. Enzyme activity is inhibited irrespective of the purity of the enzyme used or of the amount or type of template/primer or substrate present. The inhibitory effect of the drug is only observed in the presence of dithiothreitol. The primary site of action of beta-lapachone appears to be the enzyme protein, as is also borne out by the specificity of its action. Eukaryotic DNA-dependent DNA polymerase-beta, prokaryotic DNA-dependent DNA polymerase I, several other nucleic acid polymerases and some completely unrelated enzymes are not affected. Reverse transcriptase and DNA-dependent DNA polymerase-alpha may be in someway related in possessing similarly exposed '--SH structures' in their active sites. beta-lapachone thus affords a novel means of studying such interrelationships and of further characterizing enzymes.
D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000201:enzymology; D001665:Binding Sites; D002417:Cattle; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004229:Dithiothreitol / Q000494:pharmacology*; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors; D011925:Rauscher Virus / Q000201:enzymology; D012190:Retroviridae / Q000201:enzymology*; D018894:Reverse Transcriptase Inhibitors; D013379:Substrate Specificity; D013698:Templates, Genetic
D009285:Naphthoquinones; D019384:Nucleic Acid Synthesis Inhibitors; D018894:Reverse Transcriptase Inhibitors; C014638:beta-lapachone; D004257:DNA Polymerase II; D004229:Dithiothreitol