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Quadruplexes Are Everywhere…On the Other Strand Too: The i-Motif

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Handbook of Chemical Biology of Nucleic Acids

Abstract

i-Motif (the name stems from “intercalated”), also known as i-DNA, is a pH-dependent four-stranded nucleic acid structure formed by cytosine-rich sequences via hemi-protonated and intercalated C·C+ base pairs. Although this structure is favored at acidic pH, recent evidence has demonstrated its existence in vivo, stimulating the exploration of its biological roles. Before that, it was mostly regarded as a mere structural oddity, or a tool for bio- and nanotechnologies: its unique pH-sensitive nature makes it a remarkable candidate as a nanodevice and pH sensor. In this chapter, we provide a general panorama of this structure. The history and basic knowledge of i-motif are provided first. Then, we present the main characterization methods of i-motif and factors affecting i-motif stability. Following that, we focus on the applications of i-motif in nanotechnology and analytical chemistry. Last, the interaction between i-motif and ligands and the physiological roles of i-motif are briefly introduced. We argue that the i-motif, similar to its complementary G-quadruplex, is an attractive structure for multidisciplinary approaches. It serves as a basic component for various applications and has been proposed to play biological roles in vivo.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No. 22177047), State Key Laboratory of Analytical Chemistry for Life Science (5431ZZXM2202), ANR grant ANR-21-CE44-0005-01 “ICARE,” and Scientific Research Foundation for High-level Faculty, China Pharmaceutical University (3150110048).

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Authors and Affiliations

  1. State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, China

    Jean-Louis Mergny & Jun Zhou

  2. Laboratoire d’Optique et Biosciences, Ecole Polytechnique, CNRS, Inserm, Institut Polytechnique de Paris, Palaiseau cedex, France

    Jean-Louis Mergny

  3. School of Engineering, China Pharmaceutical University, Nanjing, China

    Mingpan Cheng

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  1. Jean-Louis Mergny
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  2. Mingpan Cheng
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  3. Jun Zhou
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Correspondence to Jun Zhou .

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Editors and Affiliations

  1. Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, Kobe, Japan

    Naoki Sugimoto

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  1. Physical Chemistry – Biophysical Chemistry, TU Dortmund University, Dortmund, Germany

    Roland Winter

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Mergny, JL., Cheng, M., Zhou, J. (2023). Quadruplexes Are Everywhere…On the Other Strand Too: The i-Motif. In: Sugimoto, N. (eds) Handbook of Chemical Biology of Nucleic Acids. Springer, Singapore. https://doi.org/10.1007/978-981-19-9776-1_5

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