Depsipeptide Nucleic Acids: Prebiotic Formation, Oligomerization, and Self-Assembly of a New Proto-Nucleic Acid Candidate.

The mechanism by which informational polymers first formed on the early earth is currently unknown. The RNA world hypothesis implies that RNA oligomers were produced prebiotically, before the emergence of enzymes, but the demonstration of such a process remains challenging. Alternatively, RNA may have been preceded by an earlier ancestral polymer, or proto-RNA, that had a greater propensity for self-assembly than RNA, with the eventual transition to functionally superior RNA being the result of chemical or biological evolution. We report a new class of nucleic acid analog, depsipeptide nucleic acid (DepsiPNA), which displays several properties that are attractive as a candidate for proto-RNA. The monomers of depsipeptide nucleic acids can form under plausibly prebiotic conditions. These monomers oligomerize spontaneously when dried from aqueous solutions to form nucleobase-functionalized depsipeptides. Once formed, these DepsiPNA oligomers are capable of complementary self-assembly and are resistant to hydrolysis in the assembled state. These results suggest that the initial formation of primitive, self-assembling, informational polymers on the early earth may have been relatively facile if the constraints of an RNA-first scenario are relaxed.