Differential and selective inhibition of cellular and herpes simplex virus DNA synthesis by arabinofuranosyladenine

Replication of Eukaryotic Chromosomes: A Close-up of the Replication Fork

“…and aphidicolin-like a-polymerase (60, 72) and is strongly inhibited by fJ-but not by aaraATP (70). Vaccinia DNA polymerase is sensitive to aphidicolin (72), and parvoviruses appear to use a-polymerase (93).…”

“…aAraATP inhibits a but not fJ polymerase, and aaraA inhibits cellular DNA replication in cells(70). The effect of araC and araA on initiation as compared to elongation during DNA replication in vivo is unclear(78,444).…”

Biological activities and modes of action of 9-α-d-arabinofuranosyladenine and 9-α-d-arabinofuranosyl-8-azaadenine

“…In addition to the results reported here, Derse and Cheng [31], using a sample of cu-araATP from the same batch used in this study, found no inhibition of highly purified DNA polymerases-cu and fi from HeLa cells. In contrast, Mtiller and his associates [3,11,12,14], also using a sample of cu-araATP obtained from us, reported that it was as effective as EaraATP, or more so, as an inhibitor of DNA polymerase-n from rabbit kidney cells. We cannot explain this conflicting result from Miiller's laboratory other than to speculate that it may be due to a peculiarity of the rabbit kidney enzyme or may reflect some differences in conditions of assay.…”

“…While this work was in progress, Miiller et al [3,11,12,14], using a sample of a+araATP from the same batch utilized herein, reported it to be an effective inhibitor of DNA polymerase-Lu and therefore similar in mode of action to @araATP. Our results, some of which have been reported in preliminary form [15], differ from those of Miiller and his associates and reopen the question as to the L. LEE BENNE~ et al mechanisms of action of the cY-arabinosyl compounds.…”

Chemotherapy of Viral Infections

“…Although the exact mechanism of action of ara-A has not yet been fully elucidated, current studies indicate that the biologic activity of ara-A is attributed to a phosphorylation of ara-A: ara-A is phosphorylated to its monophosphate form, ara-AMP, and ara-AMP is further phosphorylated to form ara-ADP and ara-ATP (BRINK and LE PAGE 1964a;ILAN et al 1970;LE PAGE 1970). Ara-ATP inhibits DNA synthesis of culture cells, tumor cells, and virus, either by incorporation into DNA (WAGAR et al 1971;MULLER et al 1977), or by inhibition of DNA polymerase (FURTH and COHEN 1968;YORK and LE PAGE 1966;MULLER et al 1977;DICIOCCIO and SRIVASTAVA 1977;FALKE et al 1979). Ara-ADP and ara-ATP also inhibit the activity of ribonucleotide reductase (YORK and LE PAGE 1966;MOORE and COHEN 1967;Fig.2).…”