2. Academic Validation
  3. Flexible double-headed cytosine-linked 2'-deoxycytidine nucleotides. Synthesis, polymerase incorporation to DNA and interaction with DNA methyltransferases

Flexible double-headed cytosine-linked 2'-deoxycytidine nucleotides. Synthesis, polymerase incorporation to DNA and interaction with DNA methyltransferases

  • Bioorg Med Chem. 2016 Mar 15;24(6):1268-76. doi: 10.1016/j.bmc.2016.01.057.
Pavel Kielkowski 1,  Hana Cahová 1,  Radek Pohl 1,  Michal Hocek 2
Affiliations

Affiliations

  • 1 Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nám. 2, CZ-16610 Prague 6, Czech Republic.
  • 2 Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nám. 2, CZ-16610 Prague 6, Czech Republic; Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, CZ-12843 Prague 2, Czech Republic. Electronic address: hocek@uochb.cas.cz.
PMID: 26899597 DOI: 10.1016/j.bmc.2016.01.057
Abstract

New types of double-headed 2'-deoxycytidine 5'-O-triphosphates (dC(XC)TPs) bearing another cytosine or 5-fluorocytosine linked through a flexible propargyl, homopropargyl or pent-1-ynyl linker to position 5 were prepared by the aqueous Sonogashira cross-coupling reactions of 5-iodo-dCTP with the corresponding (fluoro)cytosine-alkynes. The modified dC(XC)TPs were good substrates for DNA polymerases and were used for enzymatic synthesis of cytosine-functionalized DNA by primer extension or PCR. The cytosine- or fluorocytosine-linked DNA probes did not significantly inhibit DNA methyltransferases and did not cross-link to these proteins.

Keywords

DNA methyltransferases; DNA polymerases; Nucleosides; Nucleotides; Pyrimidines.

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