Characterization of a novel inhibitor of human DNA polymerases: 3,4,5-tri-O-galloylquinic acid.

Biochemical Pharmacology
W B ParkerY C Cheng

Abstract

Various galloyl derivatives of quinic acid were found to be inhibitors of human DNA polymerases. Among them, 3,4,5-tri-O-galloylquinic acid (TGQA) was the most potent inhibitor of DNA polymerase alpha. Under identical conditions, this compound was 60-fold more potent than aphidicolin as an inhibitor of DNA polymerase alpha. The inhibition of DNA polymerase alpha by this compound was not competitive with either the template or any of the deoxynucleoside triphosphates with a Ki of 0.28 microM. Under similar reaction conditions, DNA polymerases beta and gamma were much less sensitive to the effects of these compounds and, in contrast to the effect seen with DNA polymerase alpha, the inhibition of DNA polymerases beta and gamma by TGQA was competitive with respect to the template with Ki values of 44.4 and 7.5 microM respectively. The potency of these compounds against DNA polymerase gamma varied according to the assay conditions used. The inhibition of DNA polymerase gamma by TGQA could be increased substantially by using MnCl2 in place of MgCl2 and by including 50 mM potassium phosphate, pH 7.5, in the assay mixture. DNA polymerase beta was also more sensitive to TGQA when measured with MnCl2. However, potassium phosphate had lit...Continue Reading

References

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Citations

Jun 13, 2002·Critical Reviews in Food Science and Nutrition·Amy B Howell
Dec 10, 1999·Journal of Mass Spectrometry : JMS·P MiketovaB N Timmermann
Sep 10, 1999·Journal of Natural Products·D A SunS M Hecht
Mar 27, 2007·Journal of Agricultural and Food Chemistry·Michael N CliffordNikolai Kuhnert

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