Binding of a Designed Anti-Cancer Drug to the Central Cavity of an RNA Three-Way Junction

Authors

  • Dr. Siriporn Phongtongpasuk,

    1. Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch
    2. School of Chemistry, University of Birmingham, Edgbaston, Birmingham B152TT (UK)
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    • These authors contributed equally to this work.

  • Susann Paulus,

    1. Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch
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    • These authors contributed equally to this work.

  • Joachim Schnabl,

    1. Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch
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    • These authors contributed equally to this work.

  • Prof. Dr. Roland K. O. Sigel,

    Corresponding author
    1. Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch
    • Roland K. O. Sigel, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

      Bernhard Spingler, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

      Michael J. Hannon, School of Chemistry, University of Birmingham, Edgbaston, Birmingham B152TT (UK)

      Eva Freisinger, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

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  • Priv.-Doz. Dr. Bernhard Spingler,

    Corresponding author
    1. Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch
    • Roland K. O. Sigel, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

      Bernhard Spingler, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

      Michael J. Hannon, School of Chemistry, University of Birmingham, Edgbaston, Birmingham B152TT (UK)

      Eva Freisinger, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

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  • Prof. Dr. Michael J. Hannon,

    Corresponding author
    1. School of Chemistry, University of Birmingham, Edgbaston, Birmingham B152TT (UK)
    • Roland K. O. Sigel, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

      Bernhard Spingler, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

      Michael J. Hannon, School of Chemistry, University of Birmingham, Edgbaston, Birmingham B152TT (UK)

      Eva Freisinger, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

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  • Prof. Dr. Eva Freisinger

    Corresponding author
    1. Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch
    • Roland K. O. Sigel, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

      Bernhard Spingler, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

      Michael J. Hannon, School of Chemistry, University of Birmingham, Edgbaston, Birmingham B152TT (UK)

      Eva Freisinger, Institut für Anorganische Chemie, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich (Switzerland) http://www.chem.uzh.ch

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  • Financial support within the COST Actions D39 and CM1105, from the Swiss State Secretariat for Education and Research (E.F. and R.K.O.S.), the Swiss National Science Foundation (E.F. and R.K.O.S.), the University of Birmingham, the University of Zurich, and the Strategic Scholarships fellowships Frontier Research Networks from the Commission of Higher Education, Government of Thailand (S.P.) are gratefully acknowledged. R.K.O.S. is a recipient of an ERC Starting Grant 2010. We also thank Dr. Meitian Wan and Dr. Vincent Olieric for excellent support at the SLS synchrotron.

Abstract

original image

Getting to the heart of it: Co-crystallization of an RNA three-way junction with a cylindrical di-iron(II)-based anti-cancer drug (green) results in π-stacking interactions between the cylinder and the central base pairs of the RNA structure. The shape, size, and cationic nature of the cylinder were found to be responsible for this perfect fit. Native gel electrophoresis studies confirmed stabilization of the RNA three-way junction by the iron(II) cylinder.

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