Inhibition of mouse myeloma DNA polymerase alpha by 5-triphosphates of 1-beta-D-arabinofuranosylthymine and 1-beta-D-arabinofuranosylcytosine

J Biochem. 1978 May;83(5):1511-5. doi: 10.1093/oxfordjournals.jbchem.a132061.

Abstract

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.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytarabine / analogs & derivatives*
  • DNA Polymerase II / antagonists & inhibitors*
  • DNA, Neoplasm / biosynthesis
  • Liver / enzymology
  • Mice
  • Multiple Myeloma / enzymology*
  • Nucleic Acid Synthesis Inhibitors*
  • Structure-Activity Relationship
  • Thymine Nucleotides / pharmacology*

Substances

  • DNA, Neoplasm
  • Nucleic Acid Synthesis Inhibitors
  • Thymine Nucleotides
  • Cytarabine
  • DNA Polymerase II