GSBS Student Publications

Title

Carbonyldiphosphonate, a selective inhibitor of mammalian DNA polymerase delta

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Pharmacology; Department of Biochemistry and Molecular Pharmacology

Date

10-17-1989

Document Type

Article

Medical Subject Headings

Animals; Cattle; DNA; DNA Polymerase II; DNA Polymerase III; DNA-Directed DNA Polymerase; Diphosphonates; Exonucleases; Molecular Structure; Phosphonoacetic Acid; Poly dA-dT; Templates, Genetic

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Twenty-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.

Rights and Permissions

Citation: Biochemistry. 1989 Oct 17;28(21):8270-4.

Related Resources

Link to Article in PubMed

Journal Title

Biochemistry

PubMed ID

2557899