Inhibitory effects of 1-beta-D-arabinofuranosyl-5-styryluracil 5'-triphosphates on DNA-dependent DNA polymerases alpha and beta from developing cherry salmon (Oncorhynchus masou) testes: on the approach to the selective affinity chromatography for DNA polymerase alpha.

Starting from 1-beta-D-arabinofuranosyluracil, several 5-substituted derivatives were synthesized via 5-mercuri intermediate. The resulting nucleosides were converted into their corresponding 5'-triphosphates and examined for their inhibitory effects on DNA-dependent DNA polymerases alpha and beta from developing cherry salmon (Oncorhynchus masou) testes. The following results were obtained. All the compounds tested showed remarkable inhibitory effects on DNA polymerase alpha, but lesser extent on DNA polymerase beta. The inhibitory action of the hydrophobic 5-substituents against DNA polymerase alpha was stronger than against DNA polymerase beta. For example, Ki/Ki of 5-(E)-3-amino-styryl-Ara UTP is 0.32 and Ki/Km for pol alpha/Ki/Km for pol beta is 0.19. For that reason, we chose this compound as a candidate for a ligand which is applicable to selective affinity chromatography for DNA polymerase alpha.