31 results on '"SUTHERLAND, JOHN"'
Search Results
2. Triplet-Encoded Prebiotic RNA Aminoacylation.
- Author
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Su M, Schmitt C, Liu Z, Roberts SJ, Liu KC, Röder K, Jäschke A, Wales DJ, and Sutherland JD
- Subjects
- Aminoacylation, Base Sequence, Genetic Code, RNA, Transfer chemistry, Nucleic Acid Conformation, RNA metabolism, Amino Acyl-tRNA Synthetases metabolism
- Abstract
The encoding step of translation involves attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases, themselves the product of coded peptide synthesis. So, the question arises─before these enzymes evolved, how were primordial tRNAs selectively aminoacylated? Here, we demonstrate enzyme-free, sequence-dependent, chemoselective aminoacylation of RNA. We investigated two potentially prebiotic routes to aminoacyl-tRNA acceptor stem-overhang mimics and analyzed those oligonucleotides undergoing the most efficient aminoacylation. Overhang sequences do not significantly influence the chemoselectivity of aminoacylation by either route. For aminoacyl-transfer from a mixed anhydride donor strand, the chemoselectivity and stereoselectivity of aminoacylation depend on the terminal three base pairs of the stem. The results support early suggestions of a second genetic code in the acceptor stem.
- Published
- 2023
- Full Text
- View/download PDF
3. Potentially Prebiotic Synthesis of Aminoacyl-RNA via a Bridging Phosphoramidate-Ester Intermediate.
- Author
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Roberts SJ, Liu Z, and Sutherland JD
- Subjects
- Amides, Aminoacylation, Esters, Phosphoric Acids, RNA, Transfer chemistry, Amino Acyl-tRNA Synthetases metabolism, RNA chemistry
- Abstract
Translation according to the genetic code is made possible by selectivity both in aminoacylation of tRNA and in anticodon/codon recognition. In extant biology, tRNAs are selectively aminoacylated by enzymes using high-energy intermediates, but how this might have been achieved prior to the advent of protein synthesis has been a largely unanswered question in prebiotic chemistry. We have now elucidated a novel, prebiotically plausible stereoselective aminoacyl-RNA synthesis, which starts from RNA-amino acid phosphoramidates and proceeds via phosphoramidate-ester intermediates that subsequently undergo conversion to aminoacyl-esters by mild acid hydrolysis. The chemistry avoids the intermediacy of high-energy mixed carboxy-phosphate anhydrides and is greatly favored under eutectic conditions, which also potentially allow for the requisite pH fluctuation through the variable solubility of CO
2 in solid/liquid water.- Published
- 2022
- Full Text
- View/download PDF
4. Harnessing chemical energy for the activation and joining of prebiotic building blocks.
- Author
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Liu Z, Wu LF, Xu J, Bonfio C, Russell DA, and Sutherland JD
- Subjects
- Catalysis, Origin of Life, Phosphates, Phosphoric Acids, Peptides chemistry, RNA chemistry
- Abstract
Life is an out-of-equilibrium system sustained by a continuous supply of energy. In extant biology, the generation of the primary energy currency, adenosine 5'-triphosphate and its use in the synthesis of biomolecules require enzymes. Before their emergence, alternative energy sources, perhaps assisted by simple catalysts, must have mediated the activation of carboxylates and phosphates for condensation reactions. Here, we show that the chemical energy inherent to isonitriles can be harnessed to activate nucleoside phosphates and carboxylic acids through catalysis by acid and 4,5-dicyanoimidazole under mild aqueous conditions. Simultaneous activation of carboxylates and phosphates provides multiple pathways for the generation of reactive intermediates, including mixed carboxylic acid-phosphoric acid anhydrides, for the synthesis of peptidyl-RNAs, peptides, RNA oligomers and primordial phospholipids. Our results indicate that unified prebiotic activation chemistry could have enabled the joining of building blocks in aqueous solution from a common pool and enabled the progression of a system towards higher complexity, foreshadowing today's encapsulated peptide-nucleic acid system.
- Published
- 2020
- Full Text
- View/download PDF
5. Selective prebiotic formation of RNA pyrimidine and DNA purine nucleosides.
- Author
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Xu J, Chmela V, Green NJ, Russell DA, Janicki MJ, Góra RW, Szabla R, Bond AD, and Sutherland JD
- Subjects
- Adenosine analogs & derivatives, Adenosine chemistry, Cytidine chemistry, DNA genetics, Oxidation-Reduction radiation effects, Purine Nucleosides chemistry, Purine Nucleosides genetics, Pyrimidine Nucleosides chemistry, Pyrimidine Nucleosides genetics, RNA genetics, Uridine chemistry, DNA chemistry, Evolution, Chemical, Origin of Life, Purine Nucleosides chemical synthesis, Pyrimidine Nucleosides chemical synthesis, RNA chemistry
- Abstract
The nature of the first genetic polymer is the subject of major debate
1 . Although the 'RNA world' theory suggests that RNA was the first replicable information carrier of the prebiotic era-that is, prior to the dawn of life2,3 -other evidence implies that life may have started with a heterogeneous nucleic acid genetic system that included both RNA and DNA4 . Such a theory streamlines the eventual 'genetic takeover' of homogeneous DNA from RNA as the principal information-storage molecule, but requires a selective abiotic synthesis of both RNA and DNA building blocks in the same local primordial geochemical scenario. Here we demonstrate a high-yielding, completely stereo-, regio- and furanosyl-selective prebiotic synthesis of the purine deoxyribonucleosides: deoxyadenosine and deoxyinosine. Our synthesis uses key intermediates in the prebiotic synthesis of the canonical pyrimidine ribonucleosides (cytidine and uridine), and we show that, once generated, the pyrimidines persist throughout the synthesis of the purine deoxyribonucleosides, leading to a mixture of deoxyadenosine, deoxyinosine, cytidine and uridine. These results support the notion that purine deoxyribonucleosides and pyrimidine ribonucleosides may have coexisted before the emergence of life5 .- Published
- 2020
- Full Text
- View/download PDF
6. pH-Driven RNA Strand Separation under Prebiotically Plausible Conditions.
- Author
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Mariani A, Bonfio C, Johnson CM, and Sutherland JD
- Subjects
- Hydrogen-Ion Concentration, Nucleic Acid Conformation, Temperature, DNA chemistry, DNA Replication, Prebiotics, RNA chemistry
- Abstract
Replication of nucleic acids in the absence of genetically encoded enzymes represents a critical process for the emergence of cellular life. Repeated separation of complementary RNA strands is required to achieve multiple cycles of chemical replication, yet thermal denaturation under plausible prebiotic conditions is impaired by the high temperatures required to separate long RNA strands and by concurrent degradation pathways, the latter accelerated by divalent metal ions. Here we show how the melting temperature of oligoribonucleotide duplexes can be tuned by changes in pH, enabling the separation of RNA strands at moderate temperatures. At the same time, the risk of phosphodiester bond cleavage is reduced under the acid denaturation conditions herein described, both in the presence and in the absence of divalent metal ions. Through a combination of ultraviolet and circular dichroism thermal studies and gel electrophoresis, we demonstrate the relevance of geological pH oscillations in the context of the RNA strand separation problem. Our results reveal new insights in the field of prebiotic chemistry, supporting plausible geochemical scenarios in which non-enzymatic RNA replication might have taken place.
- Published
- 2018
- Full Text
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7. Non-Enzymatic RNA Backbone Proofreading through Energy-Dissipative Recycling.
- Author
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Mariani A and Sutherland JD
- Subjects
- Acetylation, Biopolymers chemistry, Chromatography, High Pressure Liquid, Hydrolysis, Origin of Life, Phosphates chemistry, RNA chemistry
- Abstract
Non-enzymatic oligomerization of activated ribonucleotides leads to ribonucleic acids that contain a mixture of 2',5'- and 3',5'-linkages, and overcoming this backbone heterogeneity has long been considered a major limitation to the prebiotic emergence of RNA. Herein, we demonstrate non-enzymatic chemistry that progressively converts 2',5'-linkages into 3',5'-linkages through iterative degradation and repair. The energetic costs of this proofreading are met by the hydrolytic turnover of a phosphate activating agent and an acylating agent. With multiple rounds of this energy-dissipative recycling, we show that all-3',5'-linked duplex RNA can emerge from a backbone heterogeneous mixture, thereby delineating a route that could have driven RNA evolution on the early earth., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2017
- Full Text
- View/download PDF
8. Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism.
- Author
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Patel BH, Percivalle C, Ritson DJ, Duffy CD, and Sutherland JD
- Subjects
- Cyanides chemistry, Sulfites chemistry, Cyanides metabolism, Lipids chemistry, Proteins chemistry, RNA chemistry, Sulfites metabolism
- Abstract
A minimal cell can be thought of as comprising informational, compartment-forming and metabolic subsystems. To imagine the abiotic assembly of such an overall system, however, places great demands on hypothetical prebiotic chemistry. The perceived differences and incompatibilities between these subsystems have led to the widely held assumption that one or other subsystem must have preceded the others. Here we experimentally investigate the validity of this assumption by examining the assembly of various biomolecular building blocks from prebiotically plausible intermediates and one-carbon feedstock molecules. We show that precursors of ribonucleotides, amino acids and lipids can all be derived by the reductive homologation of hydrogen cyanide and some of its derivatives, and thus that all the cellular subsystems could have arisen simultaneously through common chemistry. The key reaction steps are driven by ultraviolet light, use hydrogen sulfide as the reductant and can be accelerated by Cu(I)-Cu(II) photoredox cycling.
- Published
- 2015
- Full Text
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9. Conversion of biosynthetic precursors of RNA to those of DNA by photoredox chemistry.
- Author
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Ritson DJ and Sutherland JD
- Subjects
- Prebiotics, Systems Biology, Thymine chemistry, DNA chemistry, RNA chemistry
- Abstract
Soon after the origin of RNA-based life, depletion of prebiotically synthesised ribonucleotides would have driven the evolution of a biosynthetic pathway to these key building blocks. Ribozyme-catalysed nucleosidation-the key biosynthetic step-requires that ribose and the nucleobases are produced by abiotic chemistry and are relatively stable to the conditions of their synthesis. The most plausible prebiotic synthesis of sugars involves photoreduction of cyanohydrins by hydrogen sulphide in the presence of copper(I) cyanide, and we therefore subjected ribose to these conditions whereupon it was partially converted to 2-deoxyribose. Furthermore, a derivative of uracil is reduced under similar conditions to thymine. Thus, DNA biosynthetic precursors can be formed abiotically from those of RNA allowing for an early evolutionary transition to life based on RNA and DNA.
- Published
- 2014
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10. Solid-phase synthesis and hybrization behavior of partially 2'/3'-O-acetylated RNA oligonucleotides.
- Author
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Xu J, Duffy CD, Chan CK, and Sutherland JD
- Subjects
- Acetylation, Solid-Phase Synthesis Techniques, Oligoribonucleotides chemical synthesis, Oligoribonucleotides chemistry, RNA chemical synthesis, RNA chemistry
- Abstract
Synthesis of partially 2'/3'-O-acetylated oligoribonucleotides has been accomplished by using a 2'/3'-O-acetyl orthogonal protecting group strategy in which non-nucleophilic strong-base (DBU) labile nucleobase protecting groups and a UV-light cleavable linker were used. Strong-base stability of the photolabile linker allowed on-column nucleobase and phosphate deprotection, followed by a mild cleavage of the acetylated oligonucleotides from the solid support with UV light. Two 17nt oligonucleotides, which were synthesized possessing one specific internal 2'- or 3'-acetyl group, were used as synthetic standards in a recent report from this laboratory detailing the prebiotically plausible ligation of RNA oligonucleotides. In order to further investigate the effect of 2'/3'-O-acetyl groups on the stability of RNA duplex structure, two complementary bis-acetylated RNA oligonucleotides were also expediently obtained with the newly developed protocols. UV melting curves of 2'-O-acetylated RNA duplexes showed a consistent ~3.1 °C decrease in Tm per 2'-O-acetyl group.
- Published
- 2014
- Full Text
- View/download PDF
11. Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation.
- Author
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Bowler FR, Chan CK, Duffy CD, Gerland B, Islam S, Powner MW, Sutherland JD, and Xu J
- Subjects
- Acetylation, Biopolymers chemistry, Nuclear Magnetic Resonance, Biomolecular, Prebiotics, RNA chemistry
- Abstract
The recent synthesis of pyrimidine ribonucleoside-2',3'-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of ribonucleic acid (RNA) at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3',5'-linked RNA polymers of extant biochemistry has been lacking (previous attempts led only to short oligomers with mixed linkages). Here we show that the 2'-hydroxyl group of oligoribonucleotide-3'-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, which allows rapid and efficient template-directed ligation. The 2'-O-acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers that possess either 2'- or 3'-terminal phosphates is selective for the 2'-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2',3'-cyclic phosphates to predominantly 3',5'-linked RNA via partially 2'-O-acetylated RNA.
- Published
- 2013
- Full Text
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12. The chemical origins of life and its early evolution: an introduction.
- Author
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Lilley DM and Sutherland J
- Subjects
- Aminoacylation, Enzyme Activation, Peptidyl Transferases chemistry, RNA genetics, RNA, Catalytic chemistry, Ribonucleases chemistry, Ribosomes chemistry, Ribosomes genetics, Evolution, Molecular, Origin of Life, RNA chemistry
- Abstract
Can we look at contemporary biology and couple this with chemical insight to propose some plausible mechanisms for the origin of life on the planet? In what follows, we examine some promising chemical reactions by which the building blocks for nucleic acids might have been created about a billion years after the Earth formed. This could have led to self-assembling systems that were based on an all-RNA metabolism, where RNA is both catalytic and informational. We consider the breadth of RNA enzymes presently existing in biology, and to what extent these might have covered a wider range of chemistry in the RNA world. Ultimately, the RNA world would probably have given way to protein-based life quite quickly, and the origins of peptidyl transferase activity are discussed below.
- Published
- 2011
- Full Text
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13. A stereoelectronic effect in prebiotic nucleotide synthesis.
- Author
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Choudhary A, Kamer KJ, Powner MW, Sutherland JD, and Raines RT
- Subjects
- DNA chemistry, DNA genetics, Evolution, Chemical, Molecular Structure, Nucleic Acid Conformation, RNA Precursors chemistry, Computer Simulation, Models, Chemical, Nucleic Acids chemistry, Nucleotides chemistry, RNA chemistry, RNA genetics, RNA metabolism, Stereoisomerism
- Abstract
A plausible route for the spontaneous synthesis of an activated ribonucleotide that is poised for polymerization has been put forth (Powner et al. (2009) Nature, 459, 239-242). A key step in this route necessitates the regioselective phosphorylation of the secondary alcohol on C(3') of an anhydroarabinonucleoside in the presence of the primary alcohol on C(5'). Here, we propose that this regioselectivity relies on electron delocalization between a lone pair (n) of O(5') and an antibonding orbital (pi*) of C(2) horizontal lineN(3). This n-->pi* interaction modulates reactivity without the use of a protecting group. Thus, a stereoelectronic effect could have opened a gateway to the "RNA world", the chemical milieu from which the first forms of life are thought to have emerged on Earth some 4 billion years ago.
- Published
- 2010
- Full Text
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14. RNA: prebiotic product, or biotic invention?
- Author
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Anastasi C, Buchet FF, Crowe MA, Parkes AL, Powner MW, Smith JM, and Sutherland JD
- Subjects
- Models, Molecular, Nucleic Acid Conformation, Oligoribonucleotides chemistry, RNA biosynthesis, Ribonucleotides chemistry, Ribose, RNA chemistry
- Abstract
Spectacular advances in structural and molecular biology have added support to the 'RNA world' hypothesis, and provide a mandate for chemistry to explain how RNA might have been generated prebiotically on the early earth. Difficulties in achieving a prebiotically plausible synthesis of RNA, however, have led many to ponder the question posed in the title of this paper. Herein, we review recent experimental work on the assembly of potential RNA precursors, focusing on methods for stereoselective C-C bond construction by aldolisation and related processes. This chemistry is presented in the context of a broader picture of the potential constitutional self-assembly of RNA. Finally, the relative accessibility of RNA and alternative nucleic acids is considered.
- Published
- 2007
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15. Two-step potentially prebiotic synthesis of alpha-d-cytidine-5'-phosphate from d-glyceraldehyde-3-phosphate.
- Author
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Anastasi C, Crowe MA, and Sutherland JD
- Subjects
- Oxazoles chemistry, Cytidine Monophosphate chemical synthesis, Glyceraldehyde 3-Phosphate chemistry, RNA chemistry, Ribonucleotides chemical synthesis
- Published
- 2007
- Full Text
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16. Looking beyond the RNA structural neighborhood for potentially primordial genetic systems.
- Author
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Sutherland JD
- Subjects
- Base Pairing, Nucleic Acid Conformation, RNA chemistry, RNA genetics
- Published
- 2007
- Full Text
- View/download PDF
17. Reaction of cytidine nucleotides with cyanoacetylene: support for the intermediacy of nucleoside-2',3'-cyclic phosphates in the prebiotic synthesis of RNA.
- Author
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Crowe MA and Sutherland JD
- Subjects
- Acetylene chemistry, Alanine chemistry, Cyclization, Evolution, Molecular, Magnetic Resonance Spectroscopy, Molecular Structure, Acetylene analogs & derivatives, Cytidine chemistry, Nitriles chemistry, Nucleosides chemistry, Origin of Life, Phosphates chemistry, RNA chemical synthesis
- Abstract
A robust and prebiotically plausible synthesis of RNA is a key requirement of the "RNA World" hypothesis, but, to date, no such synthesis has been demonstrated. Monomer synthesis strategies involving attachment of preformed nucleobases to sugars have failed, and, even if activated 5'-nucleotides could be made, the hydrolysis of these intermediates in water makes their efficient oligomerisation appear unlikely. We recently reported a synthesis of cytidine-2',3'-cyclic phosphate 1 (C>p) in which the nucleobase was assembled in stages on a sugar-phosphate template. However, 2',3'-cyclic nucleotides (N>p's) also undergo hydrolysis, in this case giving a mixture of the 2'- and 3'-monophosphates. This hydrolysis has previously been seen as making the, otherwise promising, oligomerisation of N>p's seem as unlikely as that of the 5'-activated nucleotides. We now find that cyanoacetylene, the reagent used for the second stage of nucleobase assembly in the synthesis of C>p, also reverses the effect of the hydrolysis by driving efficient cyclisation of C2'p and C3'p back to C>p. Excess cyanoacetylene also derivatises the nucleobase, but this modification is reversible at neutral pH. These findings significantly strengthen the case for N>p's in a prebiotic synthesis of RNA.
- Published
- 2006
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18. Exploratory studies to investigate a linked prebiotic origin of RNA and coded peptides. 4th Communication. Further observations concerning pyrimidine nucleoside synthesis by stepwise nucleobase assembly.
- Author
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Saewan N, Crowe MA, Helliwell M, Raftery J, Chantrapromma K, and Sutherland JD
- Subjects
- Models, Molecular, Molecular Structure, Peptides chemical synthesis, RNA chemical synthesis, Peptides chemistry, Pyrimidine Nucleosides chemical synthesis, RNA chemistry
- Abstract
As part of an ongoing investigation into a possible linked origin of RNA and coded peptides, we have (further) investigated the potentially prebiotic synthesis of pyrimidine ribonucleosides (ribonucleotides), by stepwise nucleobase assembly on sugar (sugar phosphate) scaffolds. In this paper, we complete our description of this assembly process on aldopentose scaffolds. Treatment of D-ribose (14) and D-xylose (20) with cyanamide smoothly produces the furanosylamino-oxazolines 15 and 21, respectively (Schemes 1 and 3). Similar treatment of D-lyxose (26) also produces the furanosylamino-oxazoline 29, but as a minor component of an equilibrating mixture in which the pyranosylamino-oxazoline 28 predominates (Scheme 4). Treatment of the various amino-oxazolines with cyanoacetylene gives furanosylcytidines 16, 25, and 31, and the lyxopyranosylcytidine 30 (Schemes 1-4). Minor by-products of the cyanoacetylene reaction include imino lactone 17, acetals 19, 22, and 24, and cyanovinyl adducts 22 and 23 resulting from initial addition of nucleoside OH groups to the terminal acetylenic C-atom of cyanoacetylene (Schemes 2-4).
- Published
- 2005
- Full Text
- View/download PDF
19. Exploratory studies to investigate a linked prebiotic origin of RNA and coded peptides. 3rd communication. Behaviour of 5-amino-1H-imidazole-4-carbonitrile derivatives.
- Author
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Ace K and Sutherland JD
- Subjects
- Peptides genetics, Purine Nucleotides chemistry, Purine Nucleotides genetics, RNA genetics, Evolution, Chemical, Imidazoles chemistry, Peptides chemistry, RNA chemistry
- Abstract
The potentially prebiotic synthesis of pyrimidine ribonucleotides by stepwise nucleobase assembly on arabinose-3-phosphate derivatives has been demonstrated in previous work. The generation of xylose-2-phosphate derivatives by aldolisation, and the behaviour of these compounds under the conditions of pyrimidine nucleobase assembly have also been described. In this paper, the scope for generation of purine nucleotides via 3,3'-anhydro-xylo-nucleotides is investigated. In neutral D2O solution, the potential intermediate 47 (Schemes 6 and 8) undergoes H-C2 --> D-C2 exchange, but no appreciable reaction with cyanide or cyanamide occurs. The exchange chemistry expands options for purine nucleobase assembly on sugar phosphate scaffolds.
- Published
- 2004
- Full Text
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20. Exploratory studies to investigate a linked prebiotic origin of RNA and coded peptides. 2nd communication. Derivation and reactivity of xylose phosphates.
- Author
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Smith JM, Borsenberger V, Raftery J, and Sutherland JD
- Subjects
- Pentosephosphates chemistry, Peptides chemistry, Phosphates chemistry, RNA chemistry, Xylose chemistry
- Abstract
The potentially prebiotic synthesis of ribo-nucleotides by stepwise pyrimidine nucleobase assembly on arabinose-3-phosphate derivatives has been demonstrated in previous work. Consideration of the provenance of pentose phosphates, by aldolisation or sugar phosphorylation, suggested that 2-phosphate derivatives might be generated more easily than 3-phosphate derivatives. In the 2-phosphate series, nucleobase-assembly chemistry to give ribo-nucleotides/nucleic acid can be envisaged from xylo-configured starting materials. In this paper, the derivation of xylose-2-phosphate derivatives by aldol chemistry and attempts to demonstrate subsequent pyrimidine nucleobase assembly are reported.
- Published
- 2004
- Full Text
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21. Exploratory studies to investigate a linked prebiotic origin of RNA and coded peptides.
- Author
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Borsenberger V, Crowe MA, Lehbauer J, Raftery J, Helliwell M, Bhutia K, Cox T, and Sutherland JD
- Subjects
- Peptides chemistry, RNA chemistry, Evolution, Molecular, Genetic Code genetics, Peptides genetics, RNA genetics
- Abstract
An introduction to the premise that RNA and genetically coded proteins should not be viewed as etiologically discrete entities in the origin of life is presented. This premise follows from the mutual interdependence of RNA and coded proteins in biology and the lack of prebiotically plausible constitutional self-assembly processes leading to either polymeric species. The RNA:coded peptides subsystem and its informational core, the genetic code, are then analysed retrosynthetically to suggest a (replicative) synthesis involving the intermediacy of aminoacyl-RNA trimers (cf. Scheme 5). A number of potential candidate aminoacyl-RNA trimers are identified (23-26; Scheme 6) and a chemical strategy to assess their validity is outlined. Experimental investigation of potential aminoacylation chemistry, nucleobase assembly and phosphate activation rules out three of the trimers but suggests that 26 is worthy of further investigation.
- Published
- 2004
- Full Text
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22. The central dogma of biological homochirality: How does chiral information propagate in a prebiotic network?
- Author
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Ozturk, S. Furkan, Sasselov, Dimitar D., and Sutherland, John D.
- Subjects
TRANSFER RNA ,RACEMIC mixtures ,BIOMACROMOLECULES ,MOLECULAR biology ,ENANTIOSELECTIVE catalysis ,NUCLEIC acids ,RNA - Abstract
Biological systems are homochiral, raising the question of how a racemic mixture of prebiotically synthesized biomolecules could attain a homochiral state at the network level. Based on our recent results, we aim to address a related question of how chiral information might have flowed in a prebiotic network. Utilizing the crystallization properties of the central ribonucleic acid (RNA) precursor known as ribose-aminooxazoline (RAO), we showed that its homochiral crystals can be obtained from its fully racemic solution on a magnetic mineral surface due to the chiral-induced spin selectivity (CISS) effect [Ozturk et al., arXiv:2303.01394 (2023)]. Moreover, we uncovered a mechanism facilitated by the CISS effect through which chiral molecules, such as RAO, can uniformly magnetize such surfaces in a variety of planetary environments in a persistent manner [Ozturk et al., arXiv:2304.09095 (2023)]. All this is very tantalizing because recent experiments with tRNA analogs demonstrate high stereoselectivity in the attachment of L-amino acids to D-ribonucleotides, enabling the transfer of homochirality from RNA to peptides [Wu et al., J. Am. Chem. Soc. 143, 11836 (2021)]. Therefore, the biological homochirality problem may be reduced to ensuring that a single common RNA precursor (e.g., RAO) can be made homochiral. The emergence of homochirality at RAO then allows for the chiral information to propagate through RNA, then to peptides, and ultimately through enantioselective catalysis to metabolites. This directionality of the chiral information flow parallels that of the central dogma of molecular biology—the unidirectional transfer of genetic information from nucleic acids to proteins [F. H. Crick, in Symposia of the Society for Experimental Biology, Number XII: The Biological Replication of Macromolecules, edited by F. K. Sanders (Cambridge University Press, Cambridge, 1958), pp. 138-163; and F. Crick, Nature 227, 561 (1970)]. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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23. Prebiotic synthesis of dihydrouridine by photoreduction of uridine in formamide.
- Author
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Xu, Jianfeng, Janicki, Mikołaj J., Szabla, Rafał, and Sutherland, John D.
- Subjects
FORMAMIDE ,PHOTOREDUCTION ,NUCLEOSIDES ,URIDINE ,RNA ,PYRIMIDINES ,TRANSFER RNA - Abstract
In this report, we show that a very common modification (especially in tRNA), dihydrouridine, was efficiently produced by photoreduction of the canonical pyrimidine ribonucleoside, uridine in formamide. Formamide not only acts as a solvent in this reaction, but also as the reductant. The other three components of the canonical alphabet (C, A, G) remained intact under the same conditions, suggesting that dihydrouridine might have coexisted with all four canonical RNA nucleosides (C, U, A, G) at the dawn of life. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
24. Introduction: The chemical origins of life and its early evolution: an introduction
- Author
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Lilley, David M. J. and Sutherland, John
- Published
- 2011
25. Non-Enzymatic RNA Backbone Proofreading through Energy-Dissipative Recycling.
- Author
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Mariani, Angelica and Sutherland, John D.
- Subjects
OLIGOMERIZATION ,RNA analysis ,POLYMERIZATION ,HETEROGENEOUS catalysis ,HYDROLASES - Abstract
Non-enzymatic oligomerization of activated ribonucleotides leads to ribonucleic acids that contain a mixture of 2′,5′- and 3′,5′-linkages, and overcoming this backbone heterogeneity has long been considered a major limitation to the prebiotic emergence of RNA. Herein, we demonstrate non-enzymatic chemistry that progressively converts 2′,5′-linkages into 3′,5′-linkages through iterative degradation and repair. The energetic costs of this proofreading are met by the hydrolytic turnover of a phosphate activating agent and an acylating agent. With multiple rounds of this energy-dissipative recycling, we show that all-3′,5′-linked duplex RNA can emerge from a backbone heterogeneous mixture, thereby delineating a route that could have driven RNA evolution on the early earth. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
26. Origin of biological homochirality by crystallization of an RNA precursor on a magnetic surface.
- Author
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Ozturk, S. Furkan, Ziwei Liu, Sutherland, John D., and Sasselov, Dimitar D.
- Subjects
- *
CRYSTALLIZATION , *IRON oxides , *RNA - Abstract
The article discusses the origin of biological homochirality by crystallization of an RNA precursor on a magnetic surface. It discusses the importance of achieving homochirality for a high-yielding prebiotic network capable of producing functional polymers, it also studies d the spin-selective crystallization of racemic ribo-aminooxazoline (RAO), an RNA precursor, on magnetite (Fe3O4) surfaces and which demonstrated prebiotically plausible way of achieving system-level homochirality.
- Published
- 2023
- Full Text
- View/download PDF
27. Detection of Potential TNA and RNA Nucleoside Precursors in a Prebiotic Mixture by Pure Shift Diffusion-Ordered NMR Spectroscopy.
- Author
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Islam, Saidul, Aguilar, Juan A., Powner, Matthew W., Nilsson, Mathias, Morris, Gareth A., and Sutherland, John D.
- Abstract
In the context of prebiotic chemistry, one of the characteristics of mixed nitrogenous-oxygenous chemistry is its propensity to give rise to highly complex reaction mixtures. There is therefore an urgent need to develop improved spectroscopic techniques if onerous chromatographic separations are to be avoided. One potential avenue is the combination of pure shift methodology, in which NMR spectra are measured with greatly improved resolution by suppressing multiplet structure, with diffusion-ordered spectroscopy, in which NMR signals from different species are distinguished through their different rates of diffusion. Such a combination has the added advantage of working with intact mixtures, allowing analyses to be carried out without perturbing mixtures in which chemical entities are part of a network of reactions in equilibrium. As part of a systems chemistry approach towards investigating the self-assembly of potentially prebiotic small molecules, we have analysed the complex mixture arising from mixing glycolaldehyde and cyanamide, in a first application of pure shift DOSY NMR to the characterisation of a partially unknown reaction composition. The work presented illustrates the potential of pure shift DOSY to be applied to chemistries that give rise to mixtures of compounds in which the NMR signal resolution is poor. The direct formation of potential RNA and TNA nucleoside precursors, amongst other adducts, was observed. These preliminary observations may have implications for the potentially prebiotic assembly chemistry of pyrimidine threonucleotides, and therefore of TNA, by using recently reported chemistries that yield the activated pyridimidine ribonucleotides. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
28. Chemoselective Multicomponent One-Pot Assembly of Purine Precursors in Water.
- Author
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Powner, Matthew W., Sutherland, John D., and Szostak, Jack W.
- Subjects
- *
PURINES , *WATER , *PYRIMIDINE nucleotides , *PREBIOTICS , *RNA - Abstract
The recent development of a sequential, high-yielding route to activated pyrimidine nucleotides, under conditions thought to be prebiotic, is an encouraging step toward the greater goal of a plausible prebiotic pathway to RNA and the potential for an RNA world. However, this synthesis has led to a disparity in the methodology available for stepwise construction of the canonical pyrimidine and purine nucleotides. To address this problem, and further explore prebiotically accessible chemical systems, we have developed a high-yielding, aqueous, one-pot, multicomponent reaction that tethers masked-sugar moieties to prebiotically plausible purine precursors. A pH-dependent three-component reaction system has been discovered that utilizes key nucleotide synthons 2-aminooxazole and 5-aminoimidazoles, which allows the first divergent purine/pyrimidine synthesis to be proposed. Due to regiospecific aminoimidazole tethering, the pathway allows N9 purination only, thus suggesting the first prebiotically plausible mechanism for regiospecific N9 purination. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
29. Activation chemistry drives the emergence of functionalised protocells
- Author
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Bonfio, Claudia, Russell, David A, Green, Nicholas J, Mariani, Angelica, Sutherland, John D, Bonfio, Claudia [0000-0003-4160-1163], Russell, David A [0000-0002-2182-4178], Green, Nicholas J [0000-0002-3874-7359], Mariani, Angelica [0000-0002-2547-4224], Sutherland, John D [0000-0001-7099-4731], and Apollo - University of Cambridge Repository
- Subjects
chemistry.chemical_classification ,Protocell ,34 Chemical Sciences ,010405 organic chemistry ,Vesicle ,RNA ,General Chemistry ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Amino acid ,Monoacylglycerol lipase ,Chemistry ,Membrane ,chemistry ,Amphiphile ,Biophysics ,Nucleotide - Abstract
The complexity of the simplest conceivable cell suggests that the chemistry of prebiotic mixtures needs to be explored to understand the intricate network of prebiotic reactions that led to the emergence of life. Early cells probably relied upon compatible and interconnected chemistries to link RNA, peptides and membranes. Here we show that several types of vesicles, composed of prebiotically plausible mixtures of amphiphiles, spontaneously form and sustain the methyl isocyanide-mediated activation of amino acids, peptides and nucleotides. Activation chemistry also drives the advantageous conversion of reactive monoacylglycerol phosphates into inert cyclophospholipids, thus supporting their potential role as major constituents of protocells. Moreover, activation of prebiotic building blocks within fatty acid-based vesicles yields lipidated species capable of localising to and functionalising primitive membranes. Our findings describe a potentially prebiotic scenario in which the components of primitive cells undergo activation and provide new species that might have enabled an increase in the functionality of protocells., The complexity of the simplest conceivable cell suggests that the chemistry of prebiotic mixtures needs to be explored to understand the intricate network of prebiotic reactions that led to the emergence of life.
- Full Text
- View/download PDF
30. The origin of RNA precursors on exoplanets.
- Author
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Rimmer, Paul B., Jianfeng Xu, Thompson, Samantha J., Gillen, Ed, Sutherland, John D., and Queloz, Didier
- Subjects
- *
RNA , *CHEMICAL precursors , *EXTRASOLAR planets , *PYRIMIDINES , *PHOTOCHEMISTRY - Abstract
The article offers information on a study which deals with origin of RNA precursors on exoplanets. It mentions that pyrimidine RNA precursors are needed building blocks for life, and because the pathway to form these pyrimidines involves seven steps with similar photochemical rate constants. It presents information on efficiency of the bisulfite photochemistry.
- Published
- 2018
- Full Text
- View/download PDF
31. Accidents will happen.
- Author
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Sutherland, John
- Subjects
- *
RNA , *NONFICTION - Abstract
The article reviews the book "Life From an RNA World: The Ancestor Within," by Michael Yarus.
- Published
- 2010
- Full Text
- View/download PDF
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