anti-syn Unnatural Base Pair Enables Alphabet-Expanded DNA Self-Assembly.

Self-assembly properties and diversity in higher-order structures of DNA enable programmable tools to be used to construct algorithms at the molecular level. However, the utility of DNA-based programmable tools is hampered by the low orthogonality to natural nucleic acids, especially in complex molecular systems. To address this challenge, we report here the orthogonal regulation of DNA self-assembly by using an unnatural base pair (UBP) formation. Our newly designed UBP AnN:SyN is formed in combination with anti and unusual syn glycosidic conformation with high thermal stability and selectivity. Furthermore, AnC worked as a pH-sensitive artificial nucleobase, which forms a strong base pair with cytosine under a weak acidic condition (pH 6.0). The orthogonal AnN:SyN base pair functioned as a trigger for hybridization chain reaction to provide long nicked double-stranded DNA (ca. 1000 base pairs). This work represents the first example of the orthogonal DNA self-assembly that is nonreactive to natural four-letter alphabets DNA trigger and expands the types of programmable tools that work in a complex environment.

Citation

Kunihiko Morihiro, Yuya Moriyama, Yui Nemoto, Hiraki Osumi, Akimitsu Okamoto. anti-syn Unnatural Base Pair Enables Alphabet-Expanded DNA Self-Assembly. Journal of the American Chemical Society. 2021 Sep 08;143(35):14207-14217

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PMID: 34450012

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