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Cyclic Naphthalene Diimide Derivatives as Novel DNA Ligands

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Handbook of Chemical Biology of Nucleic Acids
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Abstract

Naphthalene diimide (NDI), a water-soluble cationic compound, interacts with polyanionic DNA through electrostatic interaction and the nucleobase planes through stacking interaction. Threading intercalation is a unique mechanism mediating the binding of NDI to double-stranded DNA. The two substituents of NDI are placed in the major and minor grooves and function as clamps, resulting in the formation of a stable complex. The dissociation rate constant of NDI is approximately 10 times slower than that of propidium, a classical intercalator. NDI strongly interacts with guanine (G) and binds to G-quadruplex (G4) DNA formed by the stacking of G-quartet planes, which are in turn formed by specific hydrogen bonding of four G bases. The introduction of substituents at three or four positions on the NDI backbone can result in steric hindrance, which prevents the binding of NDI to double-stranded DNA and consequently enables NDI to function as a ligand for G4 when it binds to the G-quartet plane through stacking interaction. The G4-binding properties of NDI can also be improved through the cyclization of NDI substituents. This cyclic chain prevents binding to double-stranded DNA, imparting G4 selectivity. Cyclic NDI (cNDI) that has a cyclohexyl group in the cyclic linker can specifically bind to G4, which forms in telomeric DNA and inhibits telomerase activity. Therefore, cNDI dimers are expected to identify G4 clusters. Although this is a model system, cNDI dimers exhibit a higher ability to stabilize G4 dimers and inhibit telomerase activity than do cNDI monomers.

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Takenaka, S. (2022). Cyclic Naphthalene Diimide Derivatives as Novel DNA Ligands. In: Sugimoto, N. (eds) Handbook of Chemical Biology of Nucleic Acids. Springer, Singapore. https://doi.org/10.1007/978-981-16-1313-5_31-1

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