Carbonyldiphosphonate, a selective inhibitor of mammalian DNA polymerase delta
AuthorsTalanian, Robert Vincent
Brown, Neal C.
McKenna, Charles E.
Ye, Ting Gao
Levy, Jeffrey N.
Wright, George E.
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
Department of Pharmacology
Graduate School of Biomedical Sciences
KeywordsAnimals; Cattle; DNA; DNA Polymerase II; DNA Polymerase III; DNA-Directed DNA Polymerase; Diphosphonates; Exonucleases; Molecular Structure; Phosphonoacetic Acid; Poly dA-dT; Templates, Genetic
Medicine and Health Sciences
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AbstractTwenty-three pyrophosphate analogues were screened as inhibitors of proliferating cell nuclear antigen independent DNA polymerase delta (pol delta) derived from calf thymus. Carbonyldiphosphonate (COMDP), also known as alpha-oxomethylenediphosphonate, inhibited pol delta with a potency (Ki = 1.8 microM) 20 times greater than that displayed for DNA polymerase alpha (pol alpha) derived from the same tissue. Characterization of the mechanism of inhibition of pol delta indicated that COMDP competed with the dNTP specified by the template and was not competitive with the template-primer. In the case of pol alpha, COMDP did not compete with either the dNTP or the polynucleotide substrate. COMDP inhibited the 3'----5' exonuclease activity of pol delta weakly, displaying an IC50 greater than 1 mM.
Biochemistry. 1989 Oct 17;28(21):8270-4.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/32663