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

Abstract

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 An N :Sy N is formed in combination with anti and unusual syn glycosidic conformation with high thermal stability and selectivity. Furthermore, An C 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 An N :Sy N 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.

Molecular elements: novel approaches for molecular building

“…In order to distinguish natural AT(U)GC bases from unnatural bases, Benner proposed unnatural bases as DNA's new alphabets [33]. Encouraged by the discovery of Benner's unnatural bases in the 1980s, a few groups have since made major contributions to this field [47][48][49][50][51][52][53][54]. In fact, more than 100 unnatural bases have been reported with base-pairing properties, enough to fill the elemental table (figure 2).…”

Orthogonal Amplification Circuits Composed of Acyclic Nucleic Acids Enable RNA Detection

“…Herein, we demonstrate a hybridization chain reaction (HCR) in which an input strand triggers sequential opening of two hairpin strands to generate a long duplex. This strategy is applicable in a variety of functional tools. ,,,,− We also demonstrated an orthogonal HCR circuit composed of left-handed d - a TNA and right-handed l - a TNA with the same sequences, which can be activated specifically by a TNAs with the desired chirality. These orthogonal circuits were also utilized in an OR gate by combination with SNA, which can interact with both circuits.…”

Supernatural: Artificial Nucleobases and Backbones to Program Hybridization-Based Assemblies and Circuits

“…11 Artificial nucleobases have also been used to design hybridization networks that are nonreactive to parallel networks based on the natural four-letter alphabet (Figure 1D). 12 Additionally, artificial nucleobases can be used to regulate the dynamics of Watson−Crick pairing using an azobenzene photoswitch 13 or a reversible cross-linker (Figure 1E). 14 equilibria between strands for dual pharmacophore DNAencoded libraries, 15 extending the scope of simple thymine dimerization previously used to covalently interlock DNA assemblies.…”