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Chemical Biology of Nucleic Acids pp 459–475Cite as

Peptides Targeting G-Quadruplex Structures

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Part of the book series: RNA Technologies ((RNATECHN))

Abstract

Research in recent decades has revealed that some DNA and RNA secondary structures modulate a variety of cellular events. One secondary structure, the Guanine(G)-quadruplex, also regulates various cellular events that are mostly related to serious diseases. Systems capable of controlling DNA and RNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. Because of their biological importance, many G-quadruplex-targeting compounds have been described. However, the next generation of targeting molecules should exhibit increased G-quadruplex sequence specificity, a higher structure-inducing or -collapsing ability, and a greater degree of functionality, including on–off switches of binding ability and cellular penetration. Peptides might be good candidates for these next-generation G-quadruplex-targeting molecules due to the following advantages: (1) their easy design and synthesis, (2) their ability to mimic protein–G-quadruplex interactions, (3) the possibility of employing artificial amino acids in addition to naturally occurring amino acids, and (4) the ability to combine G-quadruplex-binding sequences with other functional sequences. Accordingly, several peptide-based compounds, such as furan-based cyclic peptides, PNA-conjugated peptides, and small molecule-peptide conjugates, have been developed. In this chapter, we introduce all these peptide ligands and describe most of the approaches for targeting G-quadruplex structures. We then conclude that peptides are among the most promising functional ligands for G-quadruplexes to control various biological events in next-generation approaches.

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Acknowledgments

We apologize to those authors whose work was not cited directly owing to space limitations. We thank Ms. E. Takekawa (Konan University, Japan) for generous supports. K. U. is also grateful to the Grants-in-Aid for Scientific Research and the “Core research” project (2009–2014) from MEXT.

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Authors and Affiliations

  1. Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Kenji Usui & Arisa Okada

  2. Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan

    Kenji Usui

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  1. Kenji Usui
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Correspondence to Kenji Usui .

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  1. Institute of Chemistry/Biochemistry, Free University Berlin, Berlin, Germany

    Volker A. Erdmann

  2. Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland

    Wojciech T. Markiewicz

  3. Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland

    Jan Barciszewski

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Usui, K., Okada, A. (2014). Peptides Targeting G-Quadruplex Structures. In: Erdmann, V., Markiewicz, W., Barciszewski, J. (eds) Chemical Biology of Nucleic Acids. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54452-1_25

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