Synthesis of DNA Dumbbell Based Inhibitors for the Human DNA Methyltransferase Dnmt1

Authors

  • David Kuch Dipl.-Chem.,

    1. Center for Integrated Protein Science (CiPSM), Department of Chemistry and Biochemistry, LMU Munich, Butenandtstrasse 5–13, 81377 Munich, Germany, Fax: (+49) 89-2180-77755
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  • Lothar Schermelleh Dr.,

    1. Center for Integrated Protein Science (CiPSM), Department of Biology II, LMU Munich, Grosshadernerstrasse 2, 82152 Martinsried, Germany
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  • Susanne Manetto Dr.,

    1. Center for Integrated Protein Science (CiPSM), Department of Chemistry and Biochemistry, LMU Munich, Butenandtstrasse 5–13, 81377 Munich, Germany, Fax: (+49) 89-2180-77755
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  • Heinrich Leonhardt Prof. Dr.,

    1. Center for Integrated Protein Science (CiPSM), Department of Biology II, LMU Munich, Grosshadernerstrasse 2, 82152 Martinsried, Germany
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  • Thomas Carell Prof. Dr.

    1. Center for Integrated Protein Science (CiPSM), Department of Chemistry and Biochemistry, LMU Munich, Butenandtstrasse 5–13, 81377 Munich, Germany, Fax: (+49) 89-2180-77755
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  • We thank the Deutsche Forschungsgemeinschaft (SFB 646), Novartis, and the Fonds der Chemischen Industrie for financial support. This work was further supported by the Center for Integrated Protein Science CiPSM.

Abstract

original image

Dumbbells that block: Dnmt1 is a crucial enzyme in maintaining the methylation pattern of genes and as such is a critical element of the epigenetic programming process. DNA dumbbell constructs have been developed that inhibit Dnmt1 and have potential in the regulation of DNA methylation patterns in cells (see scheme; SAM=S-adenosylmethionine, Fl=Cy3 fluorescence label, CN=5-azadC, C-Me=5-methyldC).

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