2,6-diaminopurine promotes repair of DNA lesions under prebiotic conditions

Abstract

High-yielding and selective prebiotic syntheses of RNA and DNA nucleotides involve UV irradiation to promote the key reaction steps and eradicate biologically irrelevant isomers. While these syntheses were likely enabled by UV-rich prebiotic environment, UV-induced formation of photodamages in polymeric nucleic acids, such as cyclobutane pyrimidine dimers (CPDs), remains the key unresolved issue for the origins of RNA and DNA on Earth. Here, we demonstrate that substitution of adenine with 2,6-diaminopurine enables repair of CPDs with yields reaching 92%. This substantial self-repairing activity originates from excellent electron donating properties of 2,6-diaminopurine in nucleic acid strands. We also show that the deoxyribonucleosides of 2,6-diaminopurine and adenine can be formed under the same prebiotic conditions. Considering that 2,6-diaminopurine was previously shown to increase the rate of nonenzymatic RNA replication, this nucleobase could have played critical roles in the formation of functional and photostable RNA/DNA oligomers in UV-rich prebiotic environments.

Photochemistry of 2-thiooxazole: a plausible prebiotic precursor to RNA nucleotides

“…adenosine or 2,6-diaminopurine. 33,40 A similar sun-screening effect was recently demonstrated for 2-aminooxazole in the presence of much more photostable 2-aminoimidazole. 40 Such constraints on the synthesis and prebiotic scenario proposed by Stairs et al 35 could still enable the concomitant formation of pyrimidine and 8-oxopurine nucleotides under prebiotically plausible conditions.…”

Generative AI Design and Exploration of Nucleoside Analogs

“…Interestingly, one of the generated molecules -N2-methylguanosine-based on fine tuning on parent nucleosides occurs naturally in eukaryotic and archeal tRNAs where it is a product of a base modification introduced by specific enzyme (47). We also observe a rare nucleoside-2,6diaminopurine, so far only reported naturally in a single genome (41,42) and that has implications for understanding early evolution of life on earth (44,46). Finally, we show that focused molecular generation could also be directly leveraged to explore the molecular space around antiviral nucleosides, specifically those active against SARS-CoV-2.…”

“…This additional hydrogen bond may contribute to stability of synthetic oligonucleotides containing 2,6-diaminopurine (43). Furthermore, this nucleoside is of particular interest in prebiotic chemistry because it can be formed abiotically alongside adenine and although is rare terrestrially, it has been isolated from meteorites (44), increases the rate of non-enzymatic RNA formation (45) and has unique electron donating properties that allow it to undergo self-repair upon UV damage (46). One of the generated molecules is identical to a modified guanosine residue-N2-methyl-guanosine (Fig.…”

Sustainable solid form screening: mechanochemical control over nucleobase hydrogen-bonded organic framework polymorphism

“…36 It is also a biologically relevant nucleobase whose nucleotides are in the genomes of bacteriophages, 37 and it is of interest to the origin of life studies due to being present in meteorites. 38 This journal is © The Royal Society of Chemistry 2022 However, the solid-state chemistry of DAP is largely neglected, despite the DAP-based materials showing interesting photochemical 39 and HOF forming properties. 40,41 HOFs are polymeric supramolecular assemblies of organic molecules held together by hydrogen bonds.…”