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In this chapter supramolecular aspects of interactions with nucleic acids are discussed, addressing mostly those involving synthetic ligands. After a brief introduction into general binding modes with double-stranded helices, we discuss the interaction with natural and synthetic polyamines, which sheds light on the underlying binding mechanisms. Polyamine–aryl conjugates are shown to lead often to a more efficient cellular uptake and to an increased biological activity; they can play an important role in the stabilization of DNA quadruplexes in telomers, and offer new applications as spectrometric markers. Different cyclophanes including calixarenes were shown to allow increased selection between DNA and RNA grooves, base flipping and unfolding of double-strands, and partially may serve as gene delivery systems. Supramolecular complexes can be designed to act as allosteric systems, triggered by external changes of pH, metal ions and other guest compounds. Significant progress has been made with the use of synthetic nucleases, which are able to surpass the efficiency even of natural restriction enzymes. Finally, the spectacular advances of DNA-based bio-nanotechnology are mentioned, which can lead to novel tools for biotechnological and biomedicinal applications.

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