Inhibition of mouse myeloma DNA polymerase alpha by 5-triphosphates of 1-beta-D-arabinofuranosylthymine and 1-beta-D-arabinofuranosylcytosine.
This is the first report dealing with the effect of 1-beta-D-arabinofuranosylthymine 5'-triphosphate (araTTP), synthesized by a new method, on eukaryotic DNA polymerase [EC 2.7.7.7]. AraTTP was tested for the inhibition of DNA synthesis in vitro using highly purified mouse myeloma DNA polymerase alpha in comparison with 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (araCTP). AraTTP was found to inhibit competitively the incorporation of [3H]dTTP into DNA and non-competitively the incorporation of [3H]dCTP, while the mode of the inhibition by araCTP was non-competitive with respect to dTTP and competitive with respect to dCTP. Neither araTTP nor araCTP was utilized as a substrate in place of dTTP or dCTP in DNA synthesis by DNA polymerase alpha.
D000818:Animals; D002478:Cells, Cultured; D003561:Cytarabine / Q000031:analogs & derivatives*; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology; D051379:Mice; D009101:Multiple Myeloma / Q000201:enzymology*; D019384:Nucleic Acid Synthesis Inhibitors; D013329:Structure-Activity Relationship; D013942:Thymine Nucleotides / Q000494:pharmacology*
D004273:DNA, Neoplasm; D019384:Nucleic Acid Synthesis Inhibitors; D013942:Thymine Nucleotides; D003561:Cytarabine; D004257:DNA Polymerase II