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Synthesis of oligonucleotide inhibitors of DNA (cytosine-C5) methyltransferase containing 5-azacytosine residues at specific sites

  1. Author:
    Garcia, R. G.
    Brank, A. S.
    Christman, J. K.
    Marquez, V. E.
    Eritja, R.
  2. Author Address

    CSIC, Inst Biol Mol Barcelona, Jordi Girona 18-26, E-08034 Barcelona, Spain. CSIC, Inst Biol Mol Barcelona, E-08034 Barcelona, Spain. European Mol Biol Lab, D-69117 Heidelberg, Germany. Univ Nebraska, Ctr Med, Dept Biochem & Mol Biol, Omaha, NE 69198 USA. Univ Nebraska, Ctr Med, UNMC Eppley Canc Ctr, Omaha, NE 69198 USA. Natl Canc Inst, Ctr Canc Res, Lab Med Chem, Frederick, MD 21702 USA. Eritja R CSIC, Inst Biol Mol Barcelona, Jordi Girona 18-26, E-08034 Barcelona, Spain.
    1. Year: 2001
  1. Journal: Antisense and Nucleic Acid Drug Development
    1. 11
    2. 6
    3. Pages: 369-378
  2. Type of Article: Article
  1. Abstract:

    The incorporation of 5-azacytosine residues into DNA causes potent inhibition of DNA (Cytosine-C5) methyltransferases. The synthesis of oligodeoxyribonucleotides incorporating single or multiple 5-aza-2'-deoxycytidine residues at precise sites was undertaken to generate an array of sequences containing the reactive 5-azacytosine base as specific target sites for enzymatic methylation. Preparation of these modified oligonucleotides requires the use of 2-(p- nitrophenyl)ethyloxycarbonyl (NPEOC) groups for the protection of exocyclic amino functions. These groups are removed under mild conditions, thus avoiding conventional protocols that are detrimental to the integrity of the 5-azacytosine ring.

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