Phosphonoformate inhibits reverse transcriptase.
作者： B. Sundquist , B. Oberg
DOI: 10.1099/0022-1317-45-2-273
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摘要: SUMMARY The new antiviral substance phosphonoformate (PFA) has been tested in a cell-free system for its effect on reverse transcriptases from an avian retrovirus (avian myeloblastosis virus, AMV) and mammalian retroviruses (Rauscher leukaemia RMuLV; bovine virus; baboon endogenous simian sarcoma visna virus). observed inhibitory of PFA compared with that structurally related substance, phosphonoacetate (PAA). Phosphonoformate, at concentration IOO #M, reduced the activities all above mentioned polymerases by 90 ~o when (rA)n.(dT)10 was used as template/primer. dose-response curves AMV RMuLV primed (rA)n.(dT)lo showed to be lOOO-fold more active than PAA; RMuEV polymerase activity 5o~ after incubation o'7/zM-PFA o. 7 mM-PAA, respectively. There no difference inhibition virus-associated purified transcriptase activity. Results various synthetic templates both RNA- DNA-dependent were inhibited PFA. Ioo/tM-PFA, while PAA had effect. dependent whether Mg ~+ or Mn divalent cation assay. Phosphonoformate arrested DNA synthesis immediately being added assay system. mechanism non-competitive respect substrate template apparent constants 16 #M 9/~M,
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