title: Inhibition of reverse transcriptase activity of avian myeloblastosis virus by pyrophosphate analogues.
abstract: Several pyrophosphate analogues have been studied for their effects on avian myeloblastosis virus reverse transcriptase and on cellular DNA polymerase alpha. Examination of structure-activity relationships for these compounds revealed that two acidic groups connected by a short bridge were necessary, but not sufficient, for inhibition of the enzyme activities. Foscarnet sodium (trisodium phosphonoformate) was the most potent inhibitor of reverse transcriptase, giving non-competitive inhibition of reactions primed by (rA)n . (dT)12-18, (rC)n . (dG)12-18, (dC)n . (dG)12-18, and activated DNA. Carbonyldiphosphonate and 2-hydroxyphosphonoacetate also caused non-competitive inhibition patterns, whereas hypophosphate and imidodiphosphonate inhibited AMV reverse transcriptase in a competitive, non-linear manner. The reverse transcriptase reactions directed by (rA)n . (dT)12-18 and activated DNA were most affected by the non-competitive inhibitors. Hypophosphate and imidodiphosphonate inhibited preferentially reactions primed by (dC)n . (dG)12-18 and activated DNA. In all cases the (rC)n . (dG)12-18 directed reaction was the least affected.
mesh_terms: D001354:Avian Leukosis Virus / Q000201:enzymology*; D009189:Avian Myeloblastosis Virus / Q000201:enzymology*; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D011756:Diphosphates / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology; D017245:Foscarnet; D007700:Kinetics; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D011756:Diphosphates; D004164:Diphosphonates; D011089:Polydeoxyribonucleotides; D018894:Reverse Transcriptase Inhibitors; D017245:Foscarnet; D004257:DNA Polymerase II; D010746:Phosphonoacetic Acid