Chirality-Promoted Chemical Ligation and Reverse Transcription of Acyclic 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 acyclic nucleic acids, achiral serinol nucleic acid (SNA) and chiral acyclic l-threoninol nucleic acid (L-aTNA), induced by N-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-aTNA fragments on an L-aTNA template. Examination of L-aTNA and SNA heteroligation and the effects of chimeric template strands revealed the crucial importance of L-aTNA 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-aTNA fragments. "Reverse transcription" from template RNA to L-aTNA 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-aTNA will find applications in XNA-based in vitro selection, the creation of artificial life, and nanotechnologies.