Inhibition of in vitro DNA chain elongation of 5-trifluoromethyl-2'-deoxyuridine residue in the template.
5-Trifluoromethyl-2'-deoxyuridine (CF3dUrd) is incorporated into the DNA of mammalian cells in culture. We have synthesized oligonucleotides that allows site specific introduction of CF3dUrd residue into synthetic DNA oligonucleotide. We described here the utilization of these oligonucleotides as template for in vitro DNA synthesis. When CF3dUrd residue located at an internucleotide site in the template, the chain elongation was partially arrested one nucleotide after or before the CF3dUrd residue of template using Escherichia coli polymerase I (Klenow fragment) or human polymerase alpha (pol alpha). These results suggested that a mechanism of antitumor activity of CF3dUrd is inhibition of DNA replication.
Satake
H
H
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Takeda
S
S
Wataya
Y
Y
D001483:Base Sequence; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004926:Escherichia coli; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000378:metabolism; D013379:Substrate Specificity; D013698:Templates, Genetic; D014271:Trifluridine / Q000737:chemistry*
D009838:Oligodeoxyribonucleotides; D004259:DNA-Directed DNA Polymerase; D014271:Trifluridine