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Nucleic acids play critical roles in every step of the central dogma of molecular biology, and both DNA and RNA are important therapeutic targets. Molecular recognition of nucleic acids is a research topic of intense interest for supramolecular chemists. The limited chemical space present in nucleic acids, as well as the uniform negative charge, make achieving sequence-specific recognition especially challenging. Nonetheless, synthetic oligonucleotide, peptide, and small-molecule ligands have been developed and shown to exhibit promising biological activity. The chapter starts with an overview of the chemical properties of nucleic acids and then describes successful examples of molecular recognition by biological and synthetic receptors. The final section briefly discusses challenges and future opportunities in the field.

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