THE ENZYMATIC TERMINATION OF POLYDEOXYNUCLEOTIDES BY 2′,3′-DIDEOXYADENOSINE TRIPHOSPHATE*

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RESUMO

The nucleoside 2′,3′-dideoxyadenosine is lethal to E. coli and blocks DNA synthesis irreversibly. The hypothesis that a derived dideoxynucleoside triphosphate is incorporated terminally into the cellular DNA has been tested in an in vitro system. The triphosphate of dideoxyadenosine was synthesized and shown to inhibit the in vitro synthesis of DNA by purified E. coli DNA polymerase. The kinetics of inhibition of nucleotide incorporation and pyrophosphate exchange were studied. Early in synthesis the dideoxynucleotide is a competitive inhibitor of the enzyme. Subsequently, synthesis is almost completely arrested.

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