Keiji Murayama

We report the hybridization properties of a novel artificial nucleic acid: acyclic L-threoninol nucleic acid (L-aTNA). L-aTNA formed a more stable duplex with DNA and RNA than either D-aTNA or serinol nucleic acid (SNA) as the rigidity of the L-form was more optimal for interaction with natural nucleic acids.

The stabilities of duplexes formed by strands of novel artificial nucleic acids composed of acyclic threoninol nucleic acid (aTNA) and serinol nucleic acid (SNA) building blocks were compared with duplexes formed by the acyclic glycol nucleic acid (GNA), peptide nucleic acid (PNA), and native DNA and RNA. All acyclic nucleic acid homoduplexes examined in this study had significantly higher thermal stability than DNA and RNA duplexes. Melting temperatures of homoduplexes were in the order of aTNA

Photocontrol of duplex formation between the totally artificial serinol nucleic acid (SNA) and target RNA was made possible using a photoresponsive nucleobase 8-pyrenylvinyl adenine (^PVA). ^PVA residues in SNA can be induced to undergo intrastrand [2 + 2] photocycloaddition by 455 nm light. Effective cycloreversion of the ^PVA photodimer results from irradiation with 340 nm light. These reactions occurred in high yield, rapidly, selectively, and reversibly. When th

An artificial nucleic acid based on acyclic serinol building blocks and termed "serinol nucleic acid" (SNA) was used to construct a fluorescent probe for RNA visualization in cells. The molecular beacon (MB) composed of only SNA with a fluorophore at one terminus and a quencher at the other was resistant to enzymatic digestion, due to its unnatural acyclic scaffold. The SNA-MB could detect its complementary RNA with extremely high sensitivity; the signal-to-background (S/B) ratio was as high as

Xeno nucleic acids (XNAs) are analogues of DNA and RNA that have a non-ribose artificial scaffold. XNAs are possible prebiotic genetic carriers as well as alternative genetic systems in artificial life. In addition, XNA oligomers can be used as biological tools. Acyclic XNAs, which do not have cyclic scaffolds, are attractive due to facile their synthesis and remarkably high nuclease resistance. To maximize the performance of XNAs, a negatively charged backbone is preferable to provide sufficien

Construction of complex DNA circuits is difficult due to unintended hybridization and degradation by enzymes under biological conditions. We herein report a hybridization chain reaction (HCR) circuit composed of left-handed acyclic d-threoninol nucleic acid (d-aTNA), which is orthogonal to right-handed DNA and RNA. Because of its high thermal stability, use of an aTNA hairpin with a short 7 base-pair stem ensured clear ON–OFF control of the HCR circuit. The aTNA circuit was stable against nuclea

Evolution of xeno nucleic acid (XNA) world essentially requires template-directed synthesis of XNA polymers. In this study, we demonstrate template-directed synthesis of an acyclic XNA, acyclic L-threoninol nucleic acid (L-aTNA), via chemical ligation mediated by N-cyanoimidazole. The ligation of an L-aTNA fragment on an L-aTNA template is significantly faster and occurs in considerably higher yield than DNA ligation. Both L-aTNA ligation on a DNA template and DNA ligation on an L-aTNA template

Abstract In this account, we discuss applications of artificial nucleic acids, acyclic threoninol nucleic acid (aTNA) and serinol nucleic acid (SNA). Seesaw gate and hybridization chain reaction (HCR) circuits composed of left-handed d-aTNA operate correctly. These left-handed circuits are orthogonal to right-handed d-DNA, d-RNA, and l-aTNA, suppressing interference between the circuits. SNA, which does not have a helical preference, can be used as an interface between right- and left-handed oli

Previously, nonenzymatic primer extension reaction of <i>acyclic</i> l-threoninol nucleic acid (L-<i>a</i>TNA) was achieved in the presence of <i>N</i>-cyanoimidazole (CNIm) and Mn²⁺; however, the reaction conditions were not optimized and a mechanistic insight was not sufficient. Herein, we report investigation of the kinetics and reaction mechanism of the chemical ligation of L-<i>a</i>TNA to L-<i>a</i>TNA and of DNA to DNA. We found that Cd²⁺, Ni²⁺, and Co<sup

Wavelength-selective photo-regulation by multiple chromophores responding to different wavelengths can expand the variation of photo-manipulating systems. Herein, we report the orthogonal photo-regulation of duplex formation between serinol nucleic acid (SNA) and RNA using light-induced crosslinking reactions mediated by a new photo-reactive nucleobase 8-naphthylvinyladenine (^NV A) and previously described 8-pyrenylvinyladenine (^PV A). An intrastrand crosslink was induced i

Abstract For a signal amplification system that is orthogonal to DNA, we designed a simplified seesaw gate composed of only D‐ a TNA. This new system performed signal amplification by toehold exchange reaction just as the DNA circuit did. Moreover, the D‐ a TNA circuit was not affected by natural nucleic acids carrying sequences complementary to the D‐ a TNA. In the presence of an SNA interface, however, an RNA signal was converted to D‐ a TNA signal, resulting in successful activation of D‐ a T