TY - JOUR T1 - Fluorinated Pyrimidines JF - Molecular Pharmacology JO - Mol Pharmacol SP - 783 LP - 791 VL - 9 IS - 6 AU - HIROSI TONE AU - CHARLES HEIDELBERGER Y1 - 1973/11/01 UR - http://molpharm.aspetjournals.org/content/9/6/783.abstract N2 - The interaction of 5-trifluoromethyl-2’-deoxyuridine 5’-triphosphate (F3dThd-5'-PPP) with various DNA-directed DNA polymerases has been studied. This analogue exhibited competitive inhibition with dThd-5'-PPP for partially purified DNA polymerases from vaccinia virus-infected HeLa cells, uninfected HeLa cell cytoplasm and nuclei, and calf thymus. The inhibition produce by F3dThd-5'-PPP of the incorporation of deoxycytidine 5'-triphosphate and deoxyadenosine 5'-triphosphate was noncompetitive or mixed. The Km values for dThd-5'-PPP of vaccinia virus-induced, HeLa cell cytoplasmic, HeLa cell nuclear, and calf thynmus DNA polymerases were 3.4, 4.6, 5.1, and 10 µM, respectively. The corresponding Ki values of F3dThd-5'-PPP for these enzymes were 4.0, 8.5, 11.5, and 17 µM. F3dThd-5'-PPP was incorporated into DNA by all these DNA polymerases. This incorporation was inhibited competitively by dThd-5'-PPP. The rates of F3dThd-5'-PPP incorporation by these enzymes were slower than those of dThd-5'-PPP. The ratio of the incorporation rate of the analogue to that of dThd-5'-PPP was higher with vaccinia virus polymerase than with uninfected HeLa cell enzymes. ACKNOWLEDGMENTS We are grateful to Denise Nadeau for skilled technical assistance, and to Dr. Peter V. Danenberg for the synthesis of F3dThd-5'-PPP. ER -