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Solution Structure of a G-quadruplex Bound to the Bisquinolinium Compound Phen-DC3

Authors

  • Wan Jun Chung,

    1. School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
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    • These authors contributed equally.

  • Dr. Brahim Heddi,

    1. School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
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    • These authors contributed equally.

  • Dr. Florian Hamon,

    1. Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
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  • Dr. Marie-Paule Teulade-Fichou,

    Corresponding author
    1. Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)
    • Marie-Paule Teulade-Fichou, Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)

      Anh Tuân Phan, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)

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  • Prof. Dr. Anh Tuân Phan

    Corresponding author
    1. School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)
    • Marie-Paule Teulade-Fichou, Institut Curie, Section Recherche, CNRS, UMR 176, Université Paris-Sud, Bat. 110–112, 91405 Orsay (France)

      Anh Tuân Phan, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore)

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  • This research was supported by the Singapore Ministry of Education and Nanyang Technological University (grants to A.T.P.). Phen-DC3 is a phenanthroline dicarboxamide bisquinolinium.

Abstract

Phen-DC3 is a highly promising compound that specifically targets G-quadruplexes, with potent biological effects observed in vivo. We used NMR spectroscopy to solve the structure of the complex formed between Phen-DC3 and an intramolecular G-quadruplex derived from the c-myc promoter. Structural information revealed that Phen-DC3 interacts with the quadruplex through extensive π-stacking with guanine bases of the top G-tetrad. On the basis of our structure, modifications are proposed for the development of this compound for selective targeting of a specific G-quadruplex conformation.

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