Xeno nucleic acids (XNAs) having non-ribose scaffolds with unique supramolecular properties

DNA and RNA have significance as genetic materials, therapeutic potential, and supramolecular properties. Advances in nucleic acid chemistry have enabled large-scale synthesis of DNA and RNA oligonucleotides and oligomers of non-natural nucleic acids, including artificial nucleic acids (xeno nucleic acids; XNAs) with non-ribose scaffolds. In this feature article, we review the chemical structures of XNAs with non-ribose scaffolds, their hybridization abilities, and their unique behaviors with a particular focus on the acyclic XNAs. First, we overview XNAs with non-ribose cyclic scaffolds and then those with acyclic scaffolds by focusing on their hybridization abilities with themselves and with DNA and RNA, and discuss the unexpectedly stable homo-duplex formation of acyclic XNAs. Next, we shed light on our acyclic threoninol nucleic acid (aTNA) and serinol nucleic acid (SNA) and show their helical preferences based on their chirality, then orthogonal control of hybridization and helical amplification of achiral XNAs are demonstrated. Finally, we show non-enzymatic template-directed synthesis of L-aTNA, and the creation of an artificial genetic system with XNAs with non-ribose scaffolds is described as a future prospect.

Automated summary

DNA and RNA have significant importance as genetic material, therapeutic potential, and supramolecular properties. Xeno nucleic acids (XNAs), including artificial nucleic acids with non-ribose scaffolds, have been synthesized on a large scale due to advances in nucleic acid chemistry. This feature article reviews the chemical structures, hybridization abilities, and unique behaviors of XNAs with non-ribose scaffolds, with a focus on acyclic XNAs. The article discusses the stable homo-duplex formation of acyclic XNAs, their helical preferences based on chirality, orthogonal control of hybridization, and the creation of an artificial genetic system with XNAs as a future prospect.