The Search for a Potentially Prebiotic Synthesis of Nucleotides via Arabinose‐3‐phosphate and Its Cyanamide Derivative

Anastasi, Carole; Buchet, Fabien F.; Crowe, Michael A.; Helliwell, Madeleine; Raftery, Jim; Sutherland, John D.

doi:10.1002/chem.200701351

Cited by 25 publications

(24 citation statements)

References 17 publications

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“…2) (in ongoing work on the prebiotic synthesis of purine nucleotides, the systems chemistry of mixtures containing hydrogen cyanide, is additionally being investigated). However, we have not presumed a particular order of assembly, and have systematically investigated many options over the last decade or so (Sutherland and Whitfield 1997;Ingar et al 2003;Smith et al 2004;Smith and Sutherland 2005;Anastasi et al 2007Anastasi et al , 2008. Furthermore, aware of the potential for certain molecules to act as catalysts of reactions in which other molecules are joined, an important aspect of our approach has been the study of the chemistry of multicomponent chemical systems, including mixed oxygenous and nitrogenous chemistry (Szostak 2009).…”

Section: Recent Resultsmentioning

confidence: 99%

Ribonucleotides

Sutherland

2010

Cold Spring Harbor Perspectives in Biology

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It has normally been assumed that ribonucleotides arose on the early Earth through a process in which ribose, the nucleobases, and phosphate became conjoined. However, under plausible prebiotic conditions, condensation of nucleobases with ribose to give b-ribonucleosides is fraught with difficulties. The reaction with purine nucleobases is low-yielding and the reaction with the canonical pyrimidine nucleobases does not work at all. The reasons for these difficulties are considered and an alternative high-yielding synthesis of pyrimidine nucleotides is discussed. Fitting the new synthesis to a plausible geochemical scenario is a remaining challenge but the prospects appear good. Discovery of an improved method of purine synthesis, and an efficient means of stringing activated nucleotides together, will provide underpinning support to those theories that posit a central role for RNA in the origins of life.

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Section: Recent Resultsmentioning

confidence: 99%

Ribonucleotides

Sutherland

2010

Cold Spring Harbor Perspectives in Biology

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“…It is reasonable that this biomolecule served as basis of the first genetic organisms, as it is evolutionary ancient, able to encode information, to catalyse chemical reactions and to (self‐) replicate (Orgel, ). Although there is evidence for the formation of nucleobases under prebiotic plausible conditions, the origin of the sugar phosphate (ribose phosphate) backbone is still debated (Anastasi et al , ; Powner et al , ; Hud et al , ). To our knowledge, all extant organisms completely circumvent the synthesis of free ribose in order to generate ribose 5‐phosphate; instead, they use sugar phosphate metabolism and generate this molecule in most cases through the pentose phosphate pathway or the Calvin cycle.…”

Section: Discussionmentioning

confidence: 99%

Non‐enzymatic glycolysis and pentose phosphate pathway‐like reactions in a plausible Archean ocean

Keller

Turchyn

Ralser

2014

Molecular Systems Biology

214

217

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The reaction sequences of central metabolism, glycolysis and the pentose phosphate pathway provide essential precursors for nucleic acids, amino acids and lipids. However, their evolutionary origins are not yet understood. Here, we provide evidence that their structure could have been fundamentally shaped by the general chemical environments in earth's earliest oceans. We reconstructed potential scenarios for oceans of the prebiotic Archean based on the composition of early sediments. We report that the resultant reaction milieu catalyses the interconversion of metabolites that in modern organisms constitute glycolysis and the pentose phosphate pathway. The 29 observed reactions include the formation and/or interconversion of glucose, pyruvate, the nucleic acid precursor ribose-5-phosphate and the amino acid precursor erythrose-4-phosphate, antedating reactions sequences similar to that used by the metabolic pathways. Moreover, the Archean ocean mimetic increased the stability of the phosphorylated intermediates and accelerated the rate of intermediate reactions and pyruvate production. The catalytic capacity of the reconstructed ocean milieu was attributable to its metal content. The reactions were particularly sensitive to ferrous iron Fe(II), which is understood to have had high concentrations in the Archean oceans. These observations reveal that reaction sequences that constitute central carbon metabolism could have been constrained by the iron-rich oceanic environment of the early Archean. The origin of metabolism could thus date back to the prebiotic world.

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“…When phosphodiester coupling was attempted using freshly prepared 4 and dodecanol, only the minor α-anomer underwent coupling whereas the desired β-anomer afforded the corresponding C 1 ,C 2 cyclic phosphate 7 . 18 Although it was not noted, others appear to have encountered this problem previously. 19 The production of this undesired product is a consequence of the deleterious removal of the C 2 tert -butyldimethylsilyl (TBS) ether and subsequent intramolecular cyclization via the electrophilic iminophosphate intermediate.…”

Section: Resultsmentioning

confidence: 96%

Synthesis of Lipid-Linked Arabinofuranose Donors for Glycosyltransferases

2013

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Mycobacteria and corynebacteria use decaprenylphosphoryl-β-D-arabinofuranose (DPA) as a critical cell wall building block. Arabinofuranosyltransferases that process this substrate to mediate cell wall assembly have served as drug targets, but little is known about the substrate specificity of any of these enzymes. To probe substrate recognition of DPA analogs, we developed a general and efficient synthetic route to β-D-arabinofuranosyl phosphodiesters. In this approach, the key glycosyl phosphodiester bond-forming reaction proceeds with high β-selectivity. In addition to its stereoselectivity, our route provides the means to readily access a variety of different lipid analogs, including aliphatic and polyprenyl substrates.

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The Search for a Potentially Prebiotic Synthesis of Nucleotides via Arabinose‐3‐phosphate and Its Cyanamide Derivative

Cited by 25 publications

References 17 publications

Ribonucleotides

Ribonucleotides

Non‐enzymatic glycolysis and pentose phosphate pathway‐like reactions in a plausible Archean ocean

Synthesis of Lipid-Linked Arabinofuranose Donors for Glycosyltransferases

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