Abstract
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.
MeSH Terms
Adenosine Triphosphate/analogs & derivatives,pharmacology
Aphidicolin
Bacillus subtilis/enzymology
DNA/biosynthesis
DNA Polymerase II/antagonists & inhibitors
DNA Polymerase III/antagonists & inhibitors
Deoxyguanine Nucleotides/pharmacology
Diterpenes/pharmacology
Dose-Response Relationship, Drug
Female
Humans
Nucleic Acid Synthesis Inhibitors
Placenta/enzymology
Pregnancy
Templates, Genetic
Chemicals
Deoxyguanine Nucleotides
Diterpenes
Nucleic Acid Synthesis Inhibitors
Aphidicolin
N(2)-(4-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate
Adenosine Triphosphate
DNA
4-n-butylanilino dATP
DNA Polymerase II
DNA Polymerase III
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lee M Y
Toomey N L
Wright G E
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