3'-Deoxy-3'-fluorothymidinetriphosphate: inhibitor and terminator of DNA synthesis catalysed by DNA polymerase beta, terminal deoxynucleotidyl transferase and DNA polymerase I

Biomed Biochim Acta. 1985;44(10):K63-73.

Abstract

3'-deoxy-3'-fluorothymidine-5'-triphosphate (dFTTP) was examined with respect to its capacity to inhibit and to terminate DNA-synthesis catalysed by DNA polymerases alpha and beta, terminal deoxynucleotidyl transferase (TdT) and E. coli DNA polymerase I (Klenow fragment). In analogy with 2', 3'-dideoxythymidine-5'-triphosphate (ddTTP) it was found that DNA polymerase beta was much more sensitive to dFTTP inhibition than DNA polymerase alpha. Moreover, the activity of TdT is strongly inhibited by both dFTTP and ddTTP, whereas the two compounds displayed a lower inhibitory potency on DNA polymerase I. Except for DNA polymerase alpha, the other investigated DNA polymerases are able to incorporate dFTTP into poly (dA).oligo (dT) and oligo (dG), respectively. The specific chain-terminating activity of dFTTP has proved for DNA sequencing to be at least equivalent to ddTTP.

MeSH terms

  • Animals
  • Base Sequence
  • DNA / biosynthesis*
  • DNA Nucleotidylexotransferase / antagonists & inhibitors
  • DNA Polymerase I / antagonists & inhibitors
  • DNA Polymerase II / antagonists & inhibitors
  • Dideoxynucleotides
  • In Vitro Techniques
  • Mice
  • Oligodeoxyribonucleotides
  • Poly dA-dT
  • Thymine Nucleotides / pharmacology*

Substances

  • Dideoxynucleotides
  • Oligodeoxyribonucleotides
  • Thymine Nucleotides
  • poly (dA).oligo((d)T)
  • Poly dA-dT
  • 3'-fluorothymidine-5'-triphosphate
  • DNA
  • DNA Nucleotidylexotransferase
  • DNA Polymerase I
  • DNA Polymerase II
  • 2',3'-dideoxythymidine triphosphate