Chirality-Promoted Chemical Ligation and Reverse Transcription of <i>Acyclic</i> Threoninol Nucleic Acid

The building blocks of current life on Earth are chiral compounds, such as 2'-deoxy-D-ribose of DNA and L-amino acids with homochirality, which play an important role in various biological reactions. We investigated the effect of chirality on the template-directed chemical synthesis of nucleic acids as a model for primitive replication of genetic materials in the absence of enzymes. The efficiency of the template-directed chemical ligation of two <i>acyclic</i> nucleic acids, achiral serinol nucleic acid (SNA) and chiral <i>acyclic</i> l-threoninol nucleic acid (L-<i>a</i>TNA), induced by <i>N</i>-cyanoimidazole and a divalent metal cation, was evaluated. The chemical ligation of SNA fragments on an SNA template was much slower than the ligation of L-<i>a</i>TNA fragments on an L-<i>a</i>TNA template. Examination of L-<i>a</i>TNA and SNA heteroligation and the effects of chimeric template strands revealed the crucial importance of L-<i>a</i>TNA chirality, which induces helical propagation and fixes the local conformation of the reactive phosphate group for effective chemical ligation. DNA and RNA templates also enhanced the ligation of SNA and L-<i>a</i>TNA fragments. "Reverse transcription" from template RNA to L-<i>a</i>TNA was also demonstrated. Our findings show that scaffold chirality is crucial for chemical replication and reverse transcription in XNA-based systems. Furthermore, the reverse transcription from RNA to L-<i>a</i>TNA will find applications in XNA-based in vitro selection, the creation of artificial life, and nanotechnologies.