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We have investigated the possible role of the bis-(3' to 5')-cyclic dinucleotides UpUp and ApUp as kinetic inhibitors of the DNA dependent RNA polymerase enzyme of E>. coli, using T7 delta D111 deletion mutant DNA and several synthetic DNA polymers as templates. We have established that UpUp is a linear competitive inhibitor of the initiation phase of the polymerization (Ki = 28 microM using T7 delta D111 DNA as a template), but that it has no effect when added during the elongation phase. The compound ApUp is an inhibitor of the reaction only when poly(dA-T).poly(dA-T) is used as a template, and UpUp is an inhibitor of the reaction when poly(dA).poly(dT) was employed as the DNA template.


C Y Hsu, D Dennis. RNA polymerase: linear competitive inhibition by bis-(3' to 5')-cyclic dinucleotides,NpNp. Nucleic acids research. 1982 Sep 25;10(18):5637-47

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PMID: 7145712

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