Inhibition of bacteriophage-Q β ribonucleic acid polymerase by guanosine triphosphate analogues

Sixteen compounds related to GTP were evaluated as inhibitors of bacteriophage-Q beta poly(C)-dependent poly(G) polymerase. Non-phosphorylated compounds, including guanine, guanosine and deoxyguanosine, were inactive. Phosphorylated compounds gave significant inhibition at millimolar concentrations. For nucleotides the feature important for inhibition was the 5′-phosphate chain. Four triphosphates, XTP, ITP, 7-methyl-GTP and 2′-O-methyl-GTP, gave 50% inhibition of both the poly(C)- and poly(U2,C)-dependent reactions at concentrations from 0.1 to 5 mM. XTP was 10-fold more potent an inhibitor of the reaction with poly(U2,C) as template. None of these four compounds was able to substitute for GTP as substrate to a significant extent. The most active compound, 2′-O-methyl-GTP, was a competitive inhibitor (Ki = 0.4 mM) of GTP in the poly(C)-dependent reaction.