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Minimal nucleotide duplex formation in water through enclathration in self-assembled hosts

Abstract

Short nucleotide fragments such as mono- and dinucleotides are generally unable to form stable hydrogen-bonded base pairs or duplexes in water. Within the hydrophobic pockets of enzymes, however, even short fragments form stable duplexes to transmit genetic information. Here, we demonstrate the efficient formation of hydrogen-bonded base pairs from mononucleotides in water through enclathration in the hydrophobic cavities of self-assembled cages. Crystallographic studies and 1H- and 15N-NMR spectroscopy clearly reveals pair-selective recognition of mononucleotides and the selective formation of an anti-Hoogsteen-type base pair in the cage's cavity. Within an analogous expanded cage, dinucleotides are also found to form a stable duplex in water. These results emphasize how hydrogen-bonded base pairing is amplified in a local hydrophobic area isolated from aqueous solution.

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Figure 1: Structures of the organic pillared coordination cages 1–4.
Figure 2: 1H-NMR spectroscopic observations for the formation of the 5·6 nucleotide base pair.
Figure 3: Crystal structure of the 2(5·6) inclusion complex.
Figure 4: 1H-NMR spectroscopic observations for the formation of the duplex 3(9)2.
Figure 5: Crystal structure of [4(9)2]n.

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Acknowledgements

We thank Masaki Kawano of The University of Tokyo for help with X-ray crystallographic analysis.

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Correspondence to Makoto Fujita.

Supplementary information

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Supplementary information (PDF 2166 kb)

Supplementary Information

Crystallographic data for heteroduplex of compounds 5 and 6 inside cage 2 (CIF 78 kb)

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Crystallographic data for homoduplex of compound 9 inside cage 4 (CIF 60 kb)

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Crystallographic data for homoduplex of compound 13 inside cage 3 (CIF 24 kb)

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Sawada, T., Yoshizawa, M., Sato, S. et al. Minimal nucleotide duplex formation in water through enclathration in self-assembled hosts. Nature Chem 1, 53–56 (2009). https://doi.org/10.1038/nchem.100

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