Prebiotic Syntheses of Noncanonical Nucleosides and Nucleotides

Abstract

The origin of nucleotides is a major question in origins-of-life research. Given the central importance of RNA in biology and the influential RNA World hypothesis, a great deal of this research has focused on finding possible prebiotic syntheses of the four canonical nucleotides of coding RNA. However, the use of nucleotides in other roles across the tree of life might be evidence that nucleotides have been used in noncoding roles for even longer than RNA has been used as a genetic polymer. Likewise, it is possible that early life utilized nucleotides other than the extant nucleotides as the monomers of informational polymers. Therefore, finding plausible prebiotic syntheses of potentially ancestral noncanonical nucleotides may be of great importance for understanding the origins and early evolution of life. Experimental investigations into abiotic noncanonical nucleotide synthesis reveal that many noncanonical nucleotides and related glycosides are formed much more easily than the canonical nucleotides. An analysis of the mechanisms by which nucleosides and nucleotides form in the solution phase or in drying−heating reactions from pre-existing sugars and heterocycles suggests that a wide variety of noncanonical nucleotides and related glycosides would have been present on the prebiotic Earth, if any such molecules were present. CONTENTS 1. Introduction 4806 1.1. General Nomenclature and Definitions 4806 1.2. Challenges, Motivations, Opportunities, and Scope 4807 1.3. Defining Two Distinct Non-Enzymatic Glycosylation Reactions 4811 2. Synthesis of Noncanonical Nucleosides by Monovalent Nucleophilic Heterocycles 4812 3. Synthesis of Noncanonical Nucleosides by Divalent Nucleophilic Heterocycles 4813 4. Synthesis of Noncanonical Nucleosides by Concomitant Sugar-Nucleobase Formation 4818 5. Challenges Associated with Phosphate and the Possibility of Earlier Alternatives 4821 6. Discussion 4824 Author Information 4827 Corresponding Author 4827 Authors 4827 Notes 4827 Biographies 4827 Acknowledgments 4828 References 4828

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

“…To further reinforce its prebiotic relevance, we have shown that D could have been formed on early Earth alongside A through a transglycosylation reaction. Alternative syntheses of purine (deoxy)nucleosides raise the prospect that D might also be a product of these alternative chemistries, perhaps in more significant yields 15 , 17 , 24 , 49 , 50 . Given its only moderately lower photostability relative to A, D could survive long enough in a UV-rich environment to be incorporated into oligomers and play a further role in enzyme-free DNA self-replication.…”

‘Whole Organism’, Systems Biology, and Top-Down Criteria for Evaluating Scenarios for the Origin of Life

“…The centrality of DNA as the information storage molecule for life today is common knowledge, but that role emerged well after the IDA. Here, we simply point out that while RNA has a special role in the origin of Darwinian life, several authors have proposed that RNA and DNA may well have emerged simultaneously, perhaps forming chimeric RNA/DNA structures (see review in [ 68 ]), with a range of nucleotides having prebiotic non-coding roles [ 193 ]. We note that while catalytic DNAs have been synthesized [ 194 ], there are no DNA catalysts in living cells.…”

Urea-Assisted Synthesis and Characterization of Saponite with Different Octahedral (Mg, Zn, Ni, Co) and Tetrahedral Metals (Al, Ga, B), a Review

“…Research studies making use of the thermal decomposition of urea as a means to control the pH during the synthesis of saponites include those of Besselink et al [ 40 ], Prihod’ko et al [ 47 ], Sychev and Prihod’ko [ 37 ], Xue and Pinnavaia [ 38 ], and Yu et al [ 48 ]. Given that urea has more potential than just controlling the pH in clay mineral synthesis as it is a potential precursor of nucleobases and related molecules and a promoter of phosphorylation [ 25 , 26 , 49 ], the urea-assisted synthesis of saponites might be useful as starting point in extending research into urea assisting the synthesis of clay minerals while at the same time providing a source of precursors for nucleobases formation.…”

“…Its structure and properties make it a potentially good starting material for the synthesis of nucleobases and related molecules [25,26]. It has been shown to promote phosphorylation reactions [25,26]. Moreover, it was able to catalyze formation of saponite clays in only 20 h under relatively mild conditions [27].…”