Abstract
Hydrolyzable tannins are a class of polyphenolic compounds commonly found in natural products. In this work, we studied the in vitro inhibitory mechanism of six molecules in this class on ALKBH2, an Fe(II)/α-ketoglutarate-dependent DNA repair enzyme in the AlkB family. We determined the IC50 values of these compounds on the repair of 3-methylcytosine and 1-methyladenine, the prototypical substrates of ALKBH2. A structure-activity relationship was also observed between the strength of inhibition and the number of galloyl moieties in a molecule. In addition, we found that the inhibition by this class of polyphenolic compounds on ALKBH2 is through an iron-chelating mechanism.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase / antagonists & inhibitors*
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AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase / metabolism
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DNA Repair*
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Hydrolyzable Tannins / chemistry
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Hydrolyzable Tannins / pharmacology*
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Iron Chelating Agents / chemistry
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Iron Chelating Agents / pharmacology*
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Molecular Structure
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Hydrolyzable Tannins
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Iron Chelating Agents
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ALKBH2 protein, human
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AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase