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Inhibition of C5-cytosine-DNA-methyltransferases

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Abstract

Changes in the methylation pattern of genomic DNA, particularly hypermethylation of tumor suppressor genes, occur at early stages of tumor development. Errors in DNA methylation contribute to both initiation and progression of various cancers. This stimulates significant interest in searching for inhibitors of C5-DNA-methyltransferases (MTases). Here we review the known nucleoside mechanism-based reversible and irreversible inhibitors of the MTases, as well as non-nucleoside ones, and discuss their inhibitory mechanisms and application for MTase investigations and cancer therapy.

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Abbreviations

AdoHcy:

S-(5′-adenosyl)-L-homocysteine

AdoMet:

S-(5′-adenosyl)-L-methionine

d4HCyd:

1-(2′-deoxy-β-D-ribofuranosyl)-2-pyrimidinone

DTT:

dithiothreitol

DZdCyd:

5,6-dihydro-5-aza-2′-deoxycytidine

EGCG:

(−)-epigallocatechin-3-gallate

FdCyd:

5-fluoro-2′-deoxycytidine

MTase:

DNA-methyltransferase

NEM:

N-ethylmaleimide

P:

2-pyrimidinone

4′-SdCyd:

4′-thio-2′-deoxycytidine

sinefungin:

S-adenosyl-L-ornithine

XRSA:

X-ray structural analysis

ZCyd:

5-azacytidine

ZdCyd:

5-aza-2′-deoxycytidine

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  1. Faculty of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Russia

    O. V. Kirsanova, N. A. Cherepanova & E. S. Gromova

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  1. O. V. Kirsanova
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  2. N. A. Cherepanova
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  3. E. S. Gromova
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Correspondence to E. S. Gromova.

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Original Russian Text © O. V. Kirsanova, N. A. Cherepanova, E. S. Gromova, 2009, published in Biokhimiya, 2009, Vol. 74, No. 11, pp. 1445–1458.

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Kirsanova, O.V., Cherepanova, N.A. & Gromova, E.S. Inhibition of C5-cytosine-DNA-methyltransferases. Biochemistry Moscow 74, 1175–1186 (2009). https://doi.org/10.1134/S0006297909110017

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