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Synthesis of DNA oligos containing 2'-deoxy-2'-fluoro-D-arabinofuranosyl-5-carboxylcytosine as hTDG inhibitor.

ABSTRACT: As an important step of the active demethylation of 5-methylcytosine (5mC), human thymine DNA glycosylase (hTDG) efficiently excises 5-carboxylcytosine (5caC) from double-stranded DNA (dsDNA). Here, we present synthesis of DNA oligos containing a 2'-deoxy-2'-fluoro-D-arabinofuranosyl-5-carboxylcytidine (F-5caC) modification that act as hTDG inhibitors. The glycosylase activity assay showed that F-5caC oligos were resistant to excision by the hTDG catalytic domain (hTDG(cat), residues 111-308) and they could inhibit the excision of DNA oligos containing 5caC. The electrophoretic mobility shift assay confirmed that DNA oligos containing F-5caC could bind well with unmodified hTDG(cat) to form a stable complex, which makes it possible to obtain the crystal structure of the complex to reveal details on how hTDG(cat) recognizes the DNA substrate.

SUBMITTER: Dai Q

PROVIDER: S-EPMC3375917 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Synthesis of DNA oligos containing 2'-deoxy-2'-fluoro-D-arabinofuranosyl-5-carboxylcytosine as hTDG inhibitor.

Dai Qing Q Lu Xingyu X Zhang Liang L He Chuan C

Tetrahedron 20120414 26

As an important step of the active demethylation of 5-methylcytosine (5mC), human thymine DNA glycosylase (hTDG) efficiently excises 5-carboxylcytosine (5caC) from double-stranded DNA (dsDNA). Here, we present synthesis of DNA oligos containing a 2'-deoxy-2'-fluoro-D-arabinofuranosyl-5-carboxylcytidine (F-5caC) modification that act as hTDG inhibitors. The glycosylase activity assay showed that F-5caC oligos were resistant to excision by the hTDG catalytic domain (hTDG(cat), residues 111-308) an ...[more]

PMID: 22711938

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Dataset Information

Synthesis of DNA oligos containing 2'-deoxy-2'-fluoro-D-arabinofuranosyl-5-carboxylcytosine as hTDG inhibitor.

Publications

Synthesis of DNA oligos containing 2'-deoxy-2'-fluoro-D-arabinofuranosyl-5-carboxylcytosine as hTDG inhibitor.

Similar Datasets

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