Synthesis of potentially prebiotic RNA precursors: Cytosine and guanine derivatives

Sutherland, John D.; Whitfield, J. N.

doi:10.1016/s0040-4039(97)00055-5

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…Phosphorus is an essential constituent in biochemical molecules such as DNA, RNA, and ATP. P may have been equally important during the evolution of life on the early Earth, including the prebiotic chemistry (28,29) that led to the hypothesized RNA world precursor of the modern DNA-RNA-protein world (3). However, the limited availability of phosphate as a solute in water coupled to its low reactivity has led some to conclude that there was little P in the earliest biomolecules (1), with replacement of phosphate by glyoxylate (30) Chromatogram showing P speciation of two samples of the Coonterunah carbonate (ALS-A and ALS-B) and of a hydrothermal control sample (ALS-C).…”

Section: Discussionmentioning

confidence: 99%

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Evidence for reactive reduced phosphorus species in the early Archean ocean

Pasek

Harnmeijer

Buick

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

171

170

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It has been hypothesized that before the emergence of modern DNA-RNA-protein life, biology evolved from an "RNA world." However, synthesizing RNA and other organophosphates under plausible early Earth conditions has proved difficult, with the incorporation of phosphorus (P) causing a particular problem because phosphate, where most environmental P resides, is relatively insoluble and unreactive. Recently, it has been proposed that during the Hadean-Archean heavy bombardment by extraterrestrial impactors, meteorites would have provided reactive P in the form of the iron-nickel phosphide mineral schreibersite. This reacts in water, releasing soluble and reactive reduced P species, such as phosphite, that could then be readily incorporated into prebiotic molecules. Here, we report the occurrence of phosphite in early Archean marine carbonates at levels indicating that this was an abundant dissolved species in the ocean before 3.5 Ga. Additionally, we show that schreibersite readily reacts with an aqueous solution of glycerol to generate phosphite and the membrane biomolecule glycerol-phosphate under mild thermal conditions, with this synthesis using a mineral source of P. Phosphite derived from schreibersite was, hence, a plausible reagent in the prebiotic synthesis of phosphorylated biomolecules and was also present on the early Earth in quantities large enough to have affected the redox state of P in the ocean. Phosphorylated biomolecules like RNA may, thus, have first formed from the reaction of reduced P species with the prebiotic organic milieu on the early Earth.origin of life | prebiotic chemistry | phosphorylation | astrobiology | exobiology P hosphorus (P) is the limiting nutrient in many ecosystems; its scarcity is linked to the insoluble nature of phosphate minerals (1, 2). Phosphorus species may have been important reagents during prebiotic chemical evolution, but their presumed low abundance has presented a problem in understanding the origin of key phosphorylated biomolecules, such as RNA (3, 4). This was recognized early in the study of prebiotic chemistry, and a possible role for more reduced P compounds was suggested because these are more soluble than phosphate (5, 6). However, no potential source of reduced P was known at the time, leaving phosphate as the only available P species under typical geochemical conditions (7).Phosphide minerals such as schreibersite (Fe,Ni) 3 P are ubiquitous minor constituents of meteorites (8) and are potential sources of reduced P (9-12). Schreibersite reacts with water to release P compounds that are reduced relative to the geologically abundant P 5+ phase phosphate PO 4 3− , including P 3+ phosphite HPO 3 2− and P 1+ hypophosphite H 2 PO 2 − (9-14). Both of these compounds are significantly more soluble than phosphate in waters of neutral pH and rich in the divalent cations Ca 2+ and Mg 2+ , such as modern seawater (5). Schreibersite reaction rates indicate complete phosphide dissolution when submerged in water over about 10 y (12), implying rapid reaction with w...

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Section: Discussionmentioning

confidence: 99%

“…Production of potential monomeric precursors to RNA involves a phosphonylation step to phosphorylate the various RNA nucleobases (29,35). Attempts to perform this reaction using inorganic phosphate have only been successful in the presence of heat, urea, and/or formamide (36,37).…”

Section: Discussionmentioning

confidence: 99%

Evidence for reactive reduced phosphorus species in the early Archean ocean

Pasek

Harnmeijer

Buick

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

171

170

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“…In recent years, methods of phosphorus amide chemistry have found wide application in solving many other particular problems of oligonucleotide chemistry, for example, for the formation of 2‘,5‘-phosphodiester bonds; − design of halo-, ,, pyren-, and fluorescein-labeled oligonucleotides and longmers; lipophilic modification of oligonucleotides; and the preparation of prebiotic RNA precursors, the Park nucleotide, and some 1-, , 2-, − and 4- 439 modified oligonucleotides. The foregoing demonstrates that phosphorylation of nucleosides by ATPA and its synthetic applications can be evaluated not only as an important but also a very promising stage in the development of nucleotide chemistry.…”

Section: B Phosphorylation Of Nucleotides Formation Of Internucleotid...mentioning

confidence: 99%

Amides of Trivalent Phosphorus Acids as Phosphorylating Reagents for Proton-Donating Nucleophiles

2000

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“…Efforts to elucidate the chemical processes by which life arose on Earth suggest that ribonucleic acid (RNA) was the first biopolymer capable of sustaining Darwinian evolution [1–7] . In order to establish a plausible path to an RNA‐only system, it is critical to connect prebiotic formation of nucleosides and ribozyme evolution through development of reactions that yield activated substrates, particularly nucleoside triphosphates (rNTPs) [8–15] . Cyclic trimetaphosphate (cTmp) has been shown to be particularly promising as both a prebiotically relevant and a highly reactive substrate among polyphosphorylating reagents (Scheme 1).…”

Section: Methodsmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] In order to establish a plausible path to an RNA-only system, it is critical to connect prebiotic formation of nucleosides and ribozyme evolution through development of reactions that yield activated substrates, particularly nucleoside triphosphates (rNTPs). [8][9][10][11][12][13][14][15] Cyclic trimetaphosphate (cTmp) has been shown to be particularly promising as both a prebiotically-relevant and a highly reactive substrate among polyphosphorylating reagents. [16][17][18][19] Several reports have demonstrated that cTmp is capable of phosphorylating a number of different substrates, including nucleosides.…”

Section: Scheme 1 Triphosphorylation Of Adenosine With Ctmpmentioning

confidence: 99%

Enzymatic RNA Production from NTPs Synthesized from Nucleosides and Trimetaphosphate**

et al. 2021

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A mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high‐energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. Previous reports have demonstrated that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under prebiotically‐relevant conditions, but their reaction rates were unknown and the influence of reaction conditions not well‐characterized. Here we established a sensitive assay that allowed for the determination of second‐order rate constants for all four rNTPs, ranging from 1.7×10−6 to 6.5×10−6 M−1 s−1. The ATP reaction shows a linear dependence on pH and Mg2+, and an enthalpy of activation of 88±4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.

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Synthesis of potentially prebiotic RNA precursors: Cytosine and guanine derivatives

Cited by 6 publications

References 11 publications

Evidence for reactive reduced phosphorus species in the early Archean ocean

Evidence for reactive reduced phosphorus species in the early Archean ocean

Amides of Trivalent Phosphorus Acids as Phosphorylating Reagents for Proton-Donating Nucleophiles

Enzymatic RNA Production from NTPs Synthesized from Nucleosides and Trimetaphosphate**

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