Highly Functional Acyclic Xeno Nucleic Acids

• Published in: Bulletin of the Chemical Society of Japan Vol. 96; no. 10; pp. 1179 - 1187
• Main Authors: Murayama, Keiji, Okita, Hikari, Asanuma, Hiroyuki
• Format: Journal Article
• Language: English
• Published: Tokyo The Chemical Society of Japan 15.10.2023; Chemical Society of Japan
• Series: The Chemical Society of Japan Award for Young Chemists for 2022
• Subjects: Acids; Circuits; Deoxyribonucleic acid; DNA; Nucleic acids; Orthogonality; Ribonucleic acid; RNA; Trimers; DNA circuit; XNA; Fluorescent probe
• ISSN: 0009-2673; 1348-0634
• DOI: 10.1246/bcsj.20230188

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 oligomers, resulting in selective detection of right-handed d-RNA via left-handed d-aTNA circuits. This detection system is not affected by contamination with natural nucleic acids in bio-samples due to the orthogonality. For chemical primer extension of l-aTNA, chemical ligation by N-cyanoimidazole and a divalent metal cation was investigated. The chemical ligation of l-aTNA was significantly faster and more effective than that of DNA. The chemical primer extension of l-aTNA was achieved using a random trimer pool as ingredients, demonstrating the promise of l-aTNA-based SELEX and artificial genetic systems.