Acyclic artificial nucleic acids with phosphodiester bonds exhibit unique functions

Abstract

Artificial nucleic acids (XNAs) have potential as therapeutic agents and fluorescent probes. These acyclic nucleic acid mimics have several advantages, including facile chemical synthesis and resistance to nuclease-mediated cleavage. Here we review our recent progress on the preparation of acyclic XNAs. Acyclic D-threoninol nucleic acid (D-aTNA) forms an extremely stable homo-duplex with complementary D-aTNA, but D-aTNA does not form a stable duplex with either DNA or RNA. Serinol nucleic acid (SNA), which has nucleobases on a serinol backbone, forms stable hybrid helices with both DNA and RNA and has unique chiroptical properties. Both chirality and helicity of an SNA duplex depend on its sequence. L-aTNA, which is an enantiomer of D-aTNA, has the highest affinity for complementary DNA and RNA among these three XNAs. Attempts to apply these XNAs as drugs, fluorescent probes, and nanomaterials are underway. Although chemical differences among these XNAs are small, all have unique properties, and XNAs with different functional characteristics will be found by chemically modifying these XNAs.