Advertisement

Rational Design of an Apoptosis-Inducing Photoreactive DNA Intercalator

Authors

  • Nico Ueberschaar,

    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena (Germany)
    Search for more papers by this author
  • Dr. Hans-Martin Dahse,

    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena (Germany)
    Search for more papers by this author
  • Tom Bretschneider,

    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena (Germany)
    Search for more papers by this author
  • Prof. Dr. Christian Hertweck

    Corresponding author
    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena (Germany)
    2. Friedrich Schiller University, Jena (Germany)
    • Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena (Germany)

    Search for more papers by this author

  • We thank A. Perner for MS analysis, H. Heinecke for NMR measurements, T. Palenta for assistance in synthesis and E.-M. Neumann for assistance in biological assays. This work was supported by the Federal Ministry of Science and Technology (BMBF (Germany)).

Abstract

original image

Light on DNA intercalators: Molecular modeling and mutasynthesis were employed to rationally tailor the antitumoral agent chartreusin into a vinyl-substituted derivative. Exposure with visible light dramatically improved antiproliferative activities owing to covalent binding with DNA and induction of apoptosis. The results hold promise for a more efficient chemotherapy, in particular for selectively treating tumors with light probes.

Ancillary