Substitution of Adenine by Purine-2,6-diamine Improves the Nonenzymatic Oligomerization of Ribonucleotides on Templates Containing Thymidine

Was a Pyrimidine‐Pyrimidine Base Pair the Ancestor of Watson‐Crick Base Pairs? Insights from a Systematic Approach to the Origin of RNA

“…This change is acceptable because the NH 2 group does not interfere with forming a Watson‐Crick base pair with uracil (or a proto uracil). D is plausibly prebiotic, being found in some meteorites22 and synthesized in model prebiotic reactions,23 and has even been shown to enhance nonenzymatic template‐directed synthesis when used in place of adenine 24. Moreover, as discussed below, this base looks attractive as an intermediate between the bases of proto‐RNA and extant RNA.…”

“…That is, the polymerization of nucleosides, organized within a hexad stack by one preformed strand of the stack, would give rise to two identical strands and three strands with sequences complementary to the original template strand. Nucleobases with increased affinity for their complementary template are known to lead to higher yields and greater fidelity during nonenzymatic template‐directed RNA synthesis 20,24. It stands to reason that the hexad‐based system comprised of TAP and BA, or similar heterocycles, which can assemble even as monomers, and have more hydrogen bonding requirements, would be affected less by poor template/monomer affinity and mismatches.…”

Photostability of 2,6-diaminopurine and its 2′-deoxyriboside investigated by femtosecond transient absorption spectroscopy

“…15–17 Furthermore, it has been shown that 26DAP replaces adenine in the genome of phage S-2L of the cyanobacteria Synechococcus elongatus entirely, 15–17 and can increase the rate of nonenzymatic RNA template copying. 18 The deoxyriboside (26DAP-d) can also undergo prebiotic phosphorylation and concomitant oligomerization to form DNA, 19 which could have been key in the development of higher-order oligomeric structures. Therefore, 26DAP may be considered an important component in protecting the prebiotic genetic material, thus enhancing the photostability of higher-order DNA structures and the formation of the first DNA oligomers.…”

Modified nucleic acids: replication, evolution, and next-generation therapeutics

“…Non-enzymatic templated synthesis traditionally uses activated nucleotides or short oligonucleotide building blocks that self-organize on a template via base-paring interactions and react to polymerize. Such template copying, pioneered in the 1970s [42][43][44], has been extended to several XNA chemistries [45][46][47][48][49][50][51][52][53], often in the context of prebiotic nucleic acid replication. For example, systems for templated replication of PNA pentamers [54,55] using reductive amination are efficient enough to permit model selection experiments [56].…”