We have developed artificial acyclic nucleic acids composed of serinol derivatives as scaffolds. Recently, template-directed synthesis of acyclic L-threoninol nucleic acid (L-αTNA) could be achieved non-enzymatically via chemical ligation mediated by N-cyanoimidazole in the presence of Mn²⁺ ion. A pseudo primer extension reaction like natural polymerase was also attained non-enzymatically using a pool of random L-αTNA trimers. In this short review, we discuss the possibility of L-αTNA as a candiate of pre-RNA before RNA world by focusing on the evolution of genetic material.

  Origins-of-life hypotheses generally posit evolution from simple molecular replicators, such as RNA, to complex living systems. The understanding of how molecular replicators could have evolved on the early Earth has been advanced through theoretical research. However, experimental verification was generally hindered due to the lack of appropriate experimental systems (i.e., molecular replicators that can undergo Darwinian evolution). Here, I describe our recent approach to develop and evolve such a model replication system to illuminate possible evolutionary pathways that would have led to the emergence of complex life.

  While the homochirality of proteinogenic amino acids has been discussed for many years, the chemical evolutionary pathway of homochiral amino acids remains controversial. The complementation of homochirality in alanine (H₂N-C^αH(-R)-COOH, -R: -C^αH₂-H) provides a simple explanation of the chemical evolutionary pathway of homochiral amino acids. If the conventional side chain (-R: -C^αH₂-R') concept on the α-carbon is switched to a new side chain concept (-R') on the β-carbon (-CH₂) of L-alanine, a chemical evolutionary tree starting at proteinogenic L-alanine could be set up. In the conventionally proposed amino acid formation reactions, such as Strecker synthesis and Michael reaction, it is difficult to control the stereochemistry of all the amino acids, because these reactions include new chirality-formation steps that depend on the size of the newly formed side chain (-R'). This research proposes a reasonable and simple evolutionary scenario to homochirality in proteinogenic amino acids starting at L-alanine.