Differential inhibition of human placental DNA polymerases delta and alpha by BuPdGTP and BuAdATP.
The p-n-butylphenyl- and p-n-butylanilino- substituted analogs of dGTP and dATP, respectively, were tested as inhibitors of purified human placental DNA polymerases alpha and delta. It was observed that DNA polymerase alpha activity was potently inhibited by these analogs with I0.5 values as low as the nanomolar range, whereas DNA polymerase delta activity was poorly inhibited, with I0.5 values of ca. 100 micromolar. These results argue for a distinct identity of these two enzymes, and demonstrate the usefulness of these analogs as probes of DNA polymerase structures. In addition, these analogs provide a rapid method for the discrimination of the two enzyme activities and a means for the selective assay of DNA polymerase delta. Aphidicolin inhibited both DNA polymerases.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D016590:Aphidicolin; D001412:Bacillus subtilis / Q000201:enzymology; D004247:DNA / Q000096:biosynthesis; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors; D003848:Deoxyguanine Nucleotides / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013698:Templates, Genetic
D003848:Deoxyguanine Nucleotides; D004224:Diterpenes; D019384:Nucleic Acid Synthesis Inhibitors; D016590:Aphidicolin; C040364:N(2)-(4-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate; D000255:Adenosine Triphosphate; D004247:DNA; C047394:4-n-butylanilino dATP; D004257:DNA Polymerase II; D004258:DNA Polymerase III