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Hydrolyzable Tannins Are Iron Chelators That Inhibit DNA Repair Enzyme ALKBH2.


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)/?-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.

SUBMITTER: Chen F 

PROVIDER: S-EPMC6890495 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Hydrolyzable Tannins Are Iron Chelators That Inhibit DNA Repair Enzyme ALKBH2.

Chen Fangyi F   Tang Qi Q   Tang Qi Q   Ma Hang H   Bian Ke K   Seeram Navindra P NP   Li Deyu D  

Chemical research in toxicology 20190528 6


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 IC<sub>50</sub> 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  ...[more]

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