Inhibitory effects of various 5-halogenated derivatives of 1-.beta.-D-arabinofuranosyluracil 5'-triphosphate on DNA polymerases from murine cells and oncornavirus: substituent effects on inhibitory action

The effects of four 5-halogenated derivatives of 1- beta -D-arabinofuranosyluracil 5'-triphosphate (aUTP) on the activity of DNA polymerases from mouse cells and oncornavirus were examined. The newly synthesized and tested compounds in this study were 1- beta -D-arabinofuranosyl-5-fluorouracil 5'-triphosphate (aFUTP), 1- beta -D-arabinofuranosyl-5-chlorouracil 5'-triphosphate (aClUTP), 1- beta -D-arabinofuranosyl-5-bromouracil 5'-triphosphate (aBrUTP), and 1- beta --D-atabinofuranosyl-5-iodouracil 5'-triphosphate (aIUTP). It was concluded that both steric and hydrophobic effects of the halogen substituents were important for the inhibition of all DNA polymerases and that the effect of halogen atoms was clearly observed for DNA polymerase beta with activated DNA and for RLV DNA polymerase with (rA) sub(n) multiplied by (dT) sub(12-18).