GSBS Student Publications

Title

Carbonyldiphosphonate, a selective inhibitor of mammalian DNA polymerase delta

Publication Date

1989-10-17

UMMS Affiliation

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

Document Type

Article

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.

Source

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

Journal/Book/Conference Title

Biochemistry

Related Resources

Link to Article in PubMed

PubMed ID

2557899

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