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Inhibition of Mammalian DNA Polymerase by the 5'-Triphosphate of 9-ß-D-Arabinofuranosyladenine¹

Department of Pathology and the Department of Therapeutic Research, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104

The 5'-triphosphate of 9-ß-D-arabinofuranosyladenine (ara-ATP) was tested as a substrate or inhibitor of polynucleotide synthesis using bacterial and mammalian polymerases. The compound was inactive as a substrate for mammalian DNA polymerase, bacterial DNA polymerase, mammalian RNA polymerase, and bacterial RNA polymerase. The compound was found to inhibit DNA synthesis catalyzed by DNA polymerase obtained from both calf thymus and bovine lymphosarcoma; the results suggest a form of mixed inhibition between ara-ATP and deoxyadenosine triphosphate. No significant inhibition of Escherichia coli DNA polymerase was observed, and RNA polymerases of both bacteria and mammalian cells were not inhibited by ara-ATP. In general, ribonucleoside triphosphates did not inhibit DNA polymerase and deoxyribonucleoside triphosphates did not inhibit RNA polymerase.

¹ This investigation was supported by USPHS Grants 7005 from the National Institute of Allergy and Infectious Disease and 10390 from the National Institute of General Medical Sciences.

² Research Career Development Awardee (GM-K3-12,888) of the USPHS.

Received 9/22/66. Accepted 5/ 2/67.