5(4<i>H</i>)‐Oxazolones as Intermediates in the Carbodiimide‐ and Cyanamide‐Promoted Peptide Activations in Aqueous Solution

Danger, Grégoire; Michaut, Arthur; Bucchi, Manon; Boiteau, Laurent; Canal, Justine; Plasson, Raphaël; Pascal, Robert

doi:10.1002/ange.201207730

Cited by 7 publications

(4 citation statements)

References 36 publications

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“…This finding suggested that the reactive amino acid species is H 3 N + ‐C(RR′)‐COO − (where R and R′ represent the amino acid side chains). It has also been proposed that cyanamide can activate N ‐acyl‐α‐amino acids to form a 5(4 H )‐oxazolone intermediate that can help facilitate the coupling of sterically hindered α‐amino acids 19. In addition, cyanamide has been suggested to be influential in other important prebiotic reactions, such as the synthesis of activated pyrimidine ribonucleotides20 and 2′‐deoxynucleotides 21…”

Section: Amino Acids Dipeptides and Dkps That Were Both Identified mentioning

confidence: 99%

A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth

et al. 2014

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Following his seminal work in 1953, Stanley Miller conducted an experiment in 1958 to study the polymerization of amino acids under simulated early Earth conditions. In the experiment, Miller sparked a gas mixture of CH4, NH3, and H2O, while intermittently adding the plausible prebiotic condensing reagent cyanamide. For unknown reasons, an analysis of the samples was not reported. We analyzed the archived samples for amino acids, dipeptides, and diketopiperazines by liquid chromatography, ion mobility spectrometry, and mass spectrometry. A dozen amino acids, 10 glycine-containing dipeptides, and 3 glycine-containing diketopiperazines were detected. Miller's experiment was repeated and similar polymerization products were observed. Aqueous heating experiments indicate that Strecker synthesis intermediates play a key role in facilitating polymerization. These results highlight the potential importance of condensing reagents in generating diversity within the prebiotic chemical inventory.

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Section: Amino Acids Dipeptides and Dkps That Were Both Identified mentioning

confidence: 99%

A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth

et al. 2014

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“…The stereochemical results obtained with both enantiomers of Ac-Ala can be explained by the intermediacy of 5(4H)-oxazolone 8a (Fig. 2), which is known to undergo racemization via an aromatic tautomer 8a' [32][33][34] and was further confirmed by an H/D exchange experiment (Fig. S24).…”

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confidence: 75%

Harnessing chemical energy for the activation and joining of prebiotic building blocks

Liu

et al. 2020

Nat. Chem.

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Life is an out of equilibrium system sustained by a continuous supply of energy 1, 2 . In extant biology, the generation of the primary energy currency, adenosine 5'triphosphate (ATP), and its use in the synthesis of biomolecules require sophisticated enzymes. Before the emergence of such enzymes, 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 conditions in aqueous solution. Simultaneous activation of carboxylates and phosphates provides multiple pathways for the generation of reactive intermediates, including mixed carboxylic acidphosphoric 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 the modern encapsulated peptide-nucleic acid system.Short RNA oligomers or peptides could have formed on early Earth in dry state 3, 4 or solution phase reactions 5, 6 following the activation of nucleotide phosphates or amino acid/peptide carboxylates, respectively. While these reactions have been performed separately, the simultaneous synthesis of RNA oligomers and peptides under dry state conditions starting from mixtures of appropriate building blocks (monomers and short oligomers) has not yet been reported. In aqueous solution, high-energy molecules, such as cyanamide 7, 8 and carbonyl sulfide 9, 10 , have been shown to drive condensation reactions of

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“…[16] Preliminary experiments supported this scenario, [17] although the reaction seemed to be most favorable at acidic pH values lower than the pK 1 value of the amino acid. [19] In addition, cyanamide has been suggested to be influential in other important prebiotic reactions, such as the synthesis of activated pyrimidine ribonucleotides [20] and 2'deoxynucleotides. It has also been proposed that cyanamide can activate N-acyl-a-amino acids to form a 5(4H)-oxazolone intermediate that can help facilitate the coupling of sterically hindered a-amino acids.…”

mentioning

confidence: 99%

“…It has also been proposed that cyanamide can activate N-acyl-a-amino acids to form a 5(4H)-oxazolone intermediate that can help facilitate the coupling of sterically hindered a-amino acids. [19] In addition, cyanamide has been suggested to be influential in other important prebiotic reactions, such as the synthesis of activated pyrimidine ribonucleotides [20] and 2'deoxynucleotides. [21] Miller never carried out a detailed analysis of his 1958 cyanamide experiment, but he did measure the absorption at 280 nm when he collected various fractions during chromatographic separation of the discharge solution from the cyanamide experiment and found absorption in several samples where peptides were expected to elute.…”

mentioning

confidence: 99%

A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth

et al. 2014

View full text Add to dashboard Cite

Following his seminal work in 1953, Stanley Miller conducted an experiment in 1958 to study the polymerization of amino acids under simulated early Earth conditions. In the experiment, Miller sparked a gas mixture of CH 4 , NH 3 , and H 2 O, while intermittently adding the plausible prebiotic condensing reagent cyanamide. For unknown reasons, an analysis of the samples was not reported. We analyzed the archived samples for amino acids, dipeptides, and diketopiperazines by liquid chromatography, ion mobility spectrometry, and mass spectrometry. A dozen amino acids, 10 glycine-containing dipeptides, and 3 glycine-containing diketopiperazines were detected. Millers experiment was repeated and similar polymerization products were observed. Aqueous heating experiments indicate that Strecker synthesis intermediates play a key role in facilitating polymerization. These results highlight the potential importance of condensing reagents in generating diversity within the prebiotic chemical inventory. Scheme 1. Scheme showing the dicyandiamide-mediated reactions involved in the polymerization of amino acids. The main dipeptide formation pathway is highlighted by the bold arrow, whereby the attack of the amino acid amide on the reactive intermediate (I) first yields the peptide amide, which is then hydrolyzed [30] to give the linear dipeptide (II).

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5(4H)‐Oxazolones as Intermediates in the Carbodiimide‐ and Cyanamide‐Promoted Peptide Activations in Aqueous Solution

Cited by 7 publications

References 36 publications

A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth

A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth

Harnessing chemical energy for the activation and joining of prebiotic building blocks

A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth

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