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A Ribonucleotide ↔ Phosphoramidate Reaction Network Optimized by Computer-Aided Design

[Image: see text] A growing number of out-of-equilibrium systems have been created and investigated in chemical laboratories over the past decade. One way to achieve this is to create a reaction cycle, in which the forward reaction is driven by a chemical fuel and the backward reaction follows a dif...

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Autores principales: Englert, Andreas, Vogel, Julian F., Bergner, Tim, Loske, Jessica, von Delius, Max
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413217/
https://www.ncbi.nlm.nih.gov/pubmed/35953065
http://dx.doi.org/10.1021/jacs.2c05861
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author Englert, Andreas
Vogel, Julian F.
Bergner, Tim
Loske, Jessica
von Delius, Max
author_facet Englert, Andreas
Vogel, Julian F.
Bergner, Tim
Loske, Jessica
von Delius, Max
author_sort Englert, Andreas
collection PubMed
description [Image: see text] A growing number of out-of-equilibrium systems have been created and investigated in chemical laboratories over the past decade. One way to achieve this is to create a reaction cycle, in which the forward reaction is driven by a chemical fuel and the backward reaction follows a different pathway. Such dissipative reaction networks are still relatively rare, however, and most non-enzymatic examples are based on the carbodiimide-driven generation of carboxylic acid anhydrides. In this work, we describe a dissipative reaction network that comprises the chemically fueled formation of phosphoramidates from natural ribonucleotides (e.g., GMP or AMP) and phosphoramidate hydrolysis as a mild backward reaction. Because the individual reactions are subject to a multitude of interconnected parameters, the software-assisted tool “Design of Experiments” (DoE) was a great asset for optimizing and understanding the network. One notable insight was the stark effect of the nucleophilic catalyst 1-ethylimidazole (EtIm) on the hydrolysis rate, which is reminiscent of the action of the histidine group in phosphoramidase enzymes (e.g., HINT1). We were also able to use the reaction cycle to generate transient self-assemblies, which were characterized by dynamic light scattering (DLS), confocal microscopy (CLSM), and cryogenic transmission electron microscopy (cryo-TEM). Because these compartments are based on prebiotically plausible building blocks, our findings may have relevance for origin-of-life scenarios.
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spelling pubmed-94132172022-08-27 A Ribonucleotide ↔ Phosphoramidate Reaction Network Optimized by Computer-Aided Design Englert, Andreas Vogel, Julian F. Bergner, Tim Loske, Jessica von Delius, Max J Am Chem Soc [Image: see text] A growing number of out-of-equilibrium systems have been created and investigated in chemical laboratories over the past decade. One way to achieve this is to create a reaction cycle, in which the forward reaction is driven by a chemical fuel and the backward reaction follows a different pathway. Such dissipative reaction networks are still relatively rare, however, and most non-enzymatic examples are based on the carbodiimide-driven generation of carboxylic acid anhydrides. In this work, we describe a dissipative reaction network that comprises the chemically fueled formation of phosphoramidates from natural ribonucleotides (e.g., GMP or AMP) and phosphoramidate hydrolysis as a mild backward reaction. Because the individual reactions are subject to a multitude of interconnected parameters, the software-assisted tool “Design of Experiments” (DoE) was a great asset for optimizing and understanding the network. One notable insight was the stark effect of the nucleophilic catalyst 1-ethylimidazole (EtIm) on the hydrolysis rate, which is reminiscent of the action of the histidine group in phosphoramidase enzymes (e.g., HINT1). We were also able to use the reaction cycle to generate transient self-assemblies, which were characterized by dynamic light scattering (DLS), confocal microscopy (CLSM), and cryogenic transmission electron microscopy (cryo-TEM). Because these compartments are based on prebiotically plausible building blocks, our findings may have relevance for origin-of-life scenarios. American Chemical Society 2022-08-11 2022-08-24 /pmc/articles/PMC9413217/ /pubmed/35953065 http://dx.doi.org/10.1021/jacs.2c05861 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Englert, Andreas
Vogel, Julian F.
Bergner, Tim
Loske, Jessica
von Delius, Max
A Ribonucleotide ↔ Phosphoramidate Reaction Network Optimized by Computer-Aided Design
title A Ribonucleotide ↔ Phosphoramidate Reaction Network Optimized by Computer-Aided Design
title_full A Ribonucleotide ↔ Phosphoramidate Reaction Network Optimized by Computer-Aided Design
title_fullStr A Ribonucleotide ↔ Phosphoramidate Reaction Network Optimized by Computer-Aided Design
title_full_unstemmed A Ribonucleotide ↔ Phosphoramidate Reaction Network Optimized by Computer-Aided Design
title_short A Ribonucleotide ↔ Phosphoramidate Reaction Network Optimized by Computer-Aided Design
title_sort ribonucleotide ↔ phosphoramidate reaction network optimized by computer-aided design
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413217/
https://www.ncbi.nlm.nih.gov/pubmed/35953065
http://dx.doi.org/10.1021/jacs.2c05861
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