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G-quadruplex self-assembly regulated by Coulombic interactions

Nature Chemistry volume 1, pages 151–155 (2009)Cite this article

Abstract

Self-assembly offers the possibility to organize molecules in a given architecture through a subtle interplay between different noncovalent interactions. Although the kind of molecular association can often be predicted from information present in the individual molecules, the synthesis of supramolecular assemblies having a perfectly defined size and shape remains challenging. Here, we introduce the use of Coulombic interactions to control the supramolecular synthesis of finite, well-defined nanostructures. In particular, we demonstrate that the energy associated with the separation of ion pairs can regulate very precisely guanosine self-assembly into discrete G-quadruplexes. Assemblies comprising 8, 12, 16 or 24 guanosine molecules can be selectively and quantitatively obtained simply by tuning the stabilization of the dissociated anions in the solvent environment. Thus, factors such as solvent polarity, the nature of the anion and the cation–anion distance are shown to have a decisive role in the growth of G-quadruplexes.

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Figure 1: Self-assembly of guanosines in the presence of cations.
Figure 2: Self-assembly of G-quadruplexes as a function of solvent polarity.
Figure 3: Dissociation of the G-quadruplexes at low concentrations, and effect of the nature of the anion or traces of water.
Figure 4: A shorter cation–anion distance increases the size of the assemblies.

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References

  1. Whitesides, G. M. & Grzybowski, B. Self-assembly at all scales. Science 295, 2418–2421 (2002).

    Article  CAS  PubMed  Google Scholar 

  2. Schmittel, M. & Kalsani, V. Functional, discrete, nanoscale supramolecular assemblies. Top. Curr. Chem. 245, 1–53 (2005).

    Article  CAS  Google Scholar 

  3. Prins, L. J., De Jong, F., Timmerman, P. & Reinhoudt, D. N. An enantiomerically pure hydrogen-bonded assembly. Nature 408, 181–184 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Sato, S. et al. Fluorous nanodroplets structurally confined in an organopalladium sphere. Science 313, 1273–1276 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Sugimoto, T., Suzuki, T., Shinkai, S. & Sada, K. A double-stranded helix by complexation of two polymer chains with a helical supramolecular assembly. J. Am. Chem. Soc. 129, 270–271 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Janssen, P. G. A., Vandenbergh, J., van Dongen, J. L., Meijer, E.W. & Schenning, A. P. H. J. ssDNA templated self-assembly of chromophores. J. Am. Chem. Soc. 129, 6078–6079 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Ikeda, A., Numata, M. & Shinkai, S. A novel attempt to control the aggregation number of dendrons with a saccharide. Chem. Lett. 9, 929–930 (1999).

    Article  Google Scholar 

  8. Michelsen, U. & Hunter, C. A. Self-assembled porphyrin polymers. Angew. Chem. Int. Ed. 39, 764–767 (2000).

    Article  CAS  Google Scholar 

  9. Brunsveld, L., Folmer, B. J. B., Meijer, E. W. & Sijbesma, R. Supramolecular polymers. Chem. Rev. 101, 4071–4098 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Sundquist, W. I. & Klug, A. Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops. Nature 342, 825–829 (1989).

    Article  CAS  PubMed  Google Scholar 

  11. Huppert, J. L. Four-stranded nucleic acids: structure, function and targeting of G-quadruplexes. Chem. Soc. Rev. 37, 1375–1384 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Davis, J. T. G-quartets 40 years later: From 5′-GMP to molecular biology and supramolecular chemistry. Angew. Chem. Int. Ed. 43, 668–698 (2004).

    Article  CAS  Google Scholar 

  13. Davis, J. T. & Spada, G. P. Supramolecular architectures generated by self-assembly of guanosine derivatives. Chem. Soc. Rev. 36, 296–313 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Gu, J., Leczczynski, J. & Banal, M. A new insight into the structure and stability of Hoogsteen hydrogen-bonded G-tetrad: An ab initio SCF study. Chem. Phys. Lett. 311, 209–214 (1999).

    Article  CAS  Google Scholar 

  15. García-Arriaga, M., Hobley, G. & Rivera, J. M. Isostructural self-assembly of 2′-deoxyguanosine derivatives in aqueous and organic media. J. Am. Chem. Soc. 130, 10492–10493 (2008)

    Article  PubMed  PubMed Central  Google Scholar 

  16. Guschlbauer, W., Chantot, J. F. & Thiele, D. Four-stranded nucleic acid structures 25 years later: From guanosine gels to telomer DNA. J. Biomol. Struct. Dyn. 8, 491–511 (1990).

    Article  CAS  PubMed  Google Scholar 

  17. Gottarelli, G. et al. The self-assembly of lipophilic guanosine derivatives in solution and on solid surfaces. Chem. Eur. J. 6, 3242–3248 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Marlow, A. L. et al. Cation-templated self-assembly of a lipophilic deoxyguanosine: Solution structure of a K+-dG8 octamer. J. Org. Chem. 64, 5116–5123 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Forman, S. L., Fettinger, J. C., Pieraccini, S., Gottarelli, G. & Davis, J. T. Toward artificial ion channels: A lipophilic G-quadruplex. J. Am. Chem. Soc. 122, 4060–4067 (2000).

    Article  CAS  Google Scholar 

  20. Shi, X., Fettinger, J. C. & Davis, J. T. Homochiral G-quadruplexes with Ba2+ but not with K+: The cation programs enantiomeric self-recognition. J. Am. Chem. Soc. 123, 6738–6739 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Shi, X. et al. Lipophilic G-quadruplexes are self-assembled ion pair receptors, and the bound anion modulates the kinetic stability of these complexes. J. Am. Chem. Soc. 125, 10830–10841 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Ma, L., Iezzi, M., Kaucher, M. S., Lam, Y.-F. & Davis, J. T. Cation exchange in lipophilic G-quadruplexes: Not all ion binding sites are equal. J. Am. Chem. Soc. 128, 15269–15277 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Kaucher, M. S., Lam, Y.-F., Pieraccini, S., Gottarelli, G. & Davis, J. T. Using diffusion NMR to characterize guanosine self-association: insights into structure and mechanism. Chem. Eur. J. 11, 164–173 (2005).

    Article  Google Scholar 

  24. Prins, L. J., De Jong, F., Timmerman, P. & Reinhoudt, D. N. Noncovalent synthesis using hydrogen bonding. Angew. Chem. Int. Ed. 40, 2382 (2001).

    Article  CAS  Google Scholar 

  25. Krossing, I. & Raabe, I. Noncoordination anions—Fact or fiction? A survey of likely candidates. Angew. Chem. Int. Ed. 43, 2066–2090 (2004).

    Article  CAS  Google Scholar 

  26. Kotch, F. W. et al. Water-mediated association provides an ion pair receptor. J. Am. Chem. Soc. 125, 15140–15150 (2003).

    Article  CAS  PubMed  Google Scholar 

  27. Wüthrich, K. NMR of Proteins and Nucleic Acids 208 (Wiley, 1986).

  28. Sessler, J. L., Sathiosatham, M., Doerr, K., Lynch, V. & Abboud, K. A. A G-quartet formed in the absence of a templating metal cation: A new 8-(N,N-dimethylaniline)guanosine derivative. Angew. Chem. Int. Ed. 39, 1300–1303 (2000).

    Article  CAS  Google Scholar 

  29. Giorgi, T. et al. Supramolecular helices via self-assembly of 8-oxoguanosines. J. Am. Chem. Soc. 125, 14741–14749 (2002).

    Article  Google Scholar 

  30. Mezzina, E. et al. The self-assembly of a lipophilic guanosine nucleoside into polymeric columnar aggregates: the nucleoside structure contains sufficient information to drive the process towards a strikingly regular polymer. Chem. Eur. J. 7, 388–395 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Mariani, P., Mazabard, C., Garbesi, A. & Spada, G. P. A study of the structure of the lyomesophases formed by the dinucleoside phosphate d(GpG). An approach by x-ray diffraction and optical microscopy. J. Am. Chem. Soc. 111, 6369–6373 (1989).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors are grateful for financial support from the Council for the Chemical Sciences of the Netherlands Organization for Scientific Research (CW-NWO). D.G.-R. would like to acknowledge a Marie Curie Intraeuropean Fellowship. We would also like to thank A. de la Escosura for his help with the transmission electron microscopy, P.G.A. Janssen and T. de Greef for discussions, and G.P. Spada and G. Gottarelli for discussions and support at the beginning of this project.

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Authors and Affiliations

  1. Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, PO Box 513, Eindhoven, 5600 MB, The Netherlands

    David González-Rodríguez, Joost L. J. van Dongen, Albertus P. H. J. Schenning & E. W. Meijer

  2. Bijvoet Center for Biomolecular Research, Crystal and Structural Chemistry, Faculty of Science, Utrecht University, Padualaan 8, Utrecht, 3584 CH, The Netherlands

    Martin Lutz & Anthony L. Spek

  3. Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, Eindhoven, 5600 MB, The Netherlands

    E. W. Meijer

Authors
  1. David González-Rodríguez
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Contributions

D.G.-R. designed and performed the synthesis and experiments and wrote the paper. J.L.J.v.D. contributed to the MS experiments. M.L. and A.L.S. contributed to the X-ray structural analysis. A.P.H.J.S. and E.W.M. supervised the work.

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Correspondence to E. W. Meijer.

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Crystallographic data for the 16-mer complex formed from compound 3 and KI (CIF 102 kb)

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González-Rodríguez, D., van Dongen, J., Lutz, M. et al. G-quadruplex self-assembly regulated by Coulombic interactions. Nature Chem 1, 151–155 (2009). https://doi.org/10.1038/nchem.177

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