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Spontaneous and Selective Peptide Elongation in Water Driven by Aminoacyl Phosphate Esters and Phase Changes

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Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Am. Chem. Soc. 2023, 145, 48, 26086-26094
    Article

    Spontaneous and Selective Peptide Elongation in Water Driven by Aminoacyl Phosphate Esters and Phase Changes
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    • Kun Dai
      Kun Dai
      DFG Cluster of Excellence livMatS @FIT─Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      More by Kun Dai
    • Mahesh D. Pol
      Mahesh D. Pol
      DFG Cluster of Excellence livMatS @FIT─Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      More by Mahesh D. Pol
    • Lenard Saile
      Lenard Saile
      DFG Cluster of Excellence livMatS @FIT─Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      More by Lenard Saile
    • Arti Sharma
      Arti Sharma
      Freiburg Center for Interactive Materials and Bioinspired Technologies (FIT), University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      More by Arti Sharma
    • Bin Liu
      Bin Liu
      College of Materials and Chemical Engineering, China Three Gorges University, Yichang, Hubei 443002, China
      More by Bin Liu
    • Ralf Thomann
      Ralf Thomann
      Freiburg Center for Interactive Materials and Bioinspired Technologies (FIT), University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      Freiburg Materials Research Center (FMF), University of Freiburg, Stefan-Meier-Strasse 21, 79104 Freiburg, Germany
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      Orcidhttps://orcid.org/0000-0002-3597-6965
    • Johanna L. Trefs
      Johanna L. Trefs
      DFG Cluster of Excellence livMatS @FIT─Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      Institute of Physical Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany
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    • Danye Qiu
      Danye Qiu
      Institute of Organic Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany
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    • Sandra Moser
      Sandra Moser
      Institute of Organic Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany
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      Orcidhttps://orcid.org/0000-0003-3718-8521
    • Stefan Wiesler
      Stefan Wiesler
      Institute of Organic Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany
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    • Bizan N. Balzer
      Bizan N. Balzer
      DFG Cluster of Excellence livMatS @FIT─Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      Freiburg Materials Research Center (FMF), University of Freiburg, Stefan-Meier-Strasse 21, 79104 Freiburg, Germany
      Institute of Physical Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany
      More by Bizan N. Balzer
      Orcidhttps://orcid.org/0000-0001-6886-0857
    • Thorsten Hugel
      Thorsten Hugel
      DFG Cluster of Excellence livMatS @FIT─Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      Institute of Physical Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany
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    • Henning J. Jessen
      Henning J. Jessen
      DFG Cluster of Excellence livMatS @FIT─Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      Institute of Organic Chemistry, University of Freiburg, Albertstrasse 21, 79104 Freiburg, Germany
      More by Henning J. Jessen
      Orcidhttps://orcid.org/0000-0002-1025-9484
    • Charalampos G. Pappas*
      Charalampos G. Pappas
      DFG Cluster of Excellence livMatS @FIT─Freiburg Center for Interactive Materials and Bioinspired Technologies, University of Freiburg, Georges-Köhler-Allee 105, 79110 Freiburg, Germany
      *[email protected]
      More by Charalampos G. Pappas
      Orcidhttps://orcid.org/0000-0003-3019-9607
    Other Access OptionsSupporting Information (1)

    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2023, 145, 48, 26086–26094
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.3c07918
    Published November 22, 2023
    Copyright © 2023 American Chemical Society
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    Abstract

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    Nature chose phosphates to activate amino acids, where reactive intermediates and complex machinery drive the construction of polyamides. Outside of biology, the pathways and mechanisms that allow spontaneous and selective peptide elongation in aqueous abiotic systems remain unclear. Herein we work to uncover those pathways by following the systems chemistry of aminoacyl phosphate esters, synthetic counterparts of aminoacyl adenylates. The phosphate esters act as solubility tags, making hydrophobic amino acids and their oligomers soluble in water and enabling selective elongation and different pathways to emerge. Thus, oligomers up to dodecamers were synthesized in one flask and on the minute time scale, where consecutive additions activated autonomous phase changes. Depending on the pathway, the resulting phases initially carry nonpolar peptides and amphiphilic oligomers containing phosphate esters. During elongation and phosphate release, shorter oligomers dominate in solution, while the aggregated phase favors the presence of longer oligomers due to their self-assembly propensity. Furthermore we demonstrated that the solution phases can be isolated and act as a new environment for continuous elongation, by adding various phosphate esters. These findings suggest that the systems chemistry of aminoacyl phosphate esters can activate a selection mechanism for peptide bond formation by merging aqueous synthesis and self-assembly.

    Copyright © 2023 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.3c07918.

    • Materials and methods description and additional UPLC chromatograms, LC–MS analysis, atomic force and transmission electron microscopy images, and peptide library characterization using circular dichroism, rheology, NMR, and turbidity measurements (PDF)

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    This article is cited by 18 publications.

    1. Mahesh D. Pol, Ralf Thomann, Yi Thomann, Charalampos G. Pappas. Abiotic Acyl Transfer Cascades Driven by Aminoacyl Phosphate Esters and Self-Assembly. Journal of the American Chemical Society 2024, 146 (43) , 29621-29629. https://doi.org/10.1021/jacs.4c10082
    2. Priyanka, Subhabrata Maiti. Probing Phoretic Transport of Oxidative Enzyme-Bound Zn(II)-Metallomicelle in Adenosine Triphosphate Gradient via a Spatially Relocated Biocatalytic Zone. Langmuir 2024, 40 (36) , 18906-18916. https://doi.org/10.1021/acs.langmuir.4c01401
    3. Soumili Roy, Janmejay Laha, Antara Reja, Dibyendu Das. Allosteric Control of the Catalytic Properties of Dipeptide-Based Supramolecular Assemblies. Journal of the American Chemical Society 2024, 146 (32) , 22522-22529. https://doi.org/10.1021/jacs.4c06447
    4. Jiarong Wu, Jake L. Greenfield. Photoswitchable Imines Drive Dynamic Covalent Systems to Nonequilibrium Steady States. Journal of the American Chemical Society 2024, 146 (30) , 20720-20727. https://doi.org/10.1021/jacs.4c03817
    5. Arti Sharma, Kun Dai, Mahesh D. Pol, Ralf Thomann, Yi Thomann, Subhra Kanti Roy, Charalampos G. Pappas. Selective peptide bond formation via side chain reactivity and self-assembly of abiotic phosphates. Nature Communications 2025, 16 (1) https://doi.org/10.1038/s41467-025-56432-6
    6. Syed Pavel Afrose, Soumili Roy, Pratip Bhattacharyya, Ajeet Kumar Singh, Lisa Roy, Dibyendu Das. Minimal catalytic dissipative assemblies via cooperation of an amino acid, a nucleobase precursor and a cofactor. Chemical Science 2025, 16 (18) , 7838-7846. https://doi.org/10.1039/D5SC00827A
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    8. Yeonsoo Lim, Gyunam Park, Hojin An, Jonghwa Han, Joonhyun Bae, Ji‐Hyun Kim, Yan Lee, Kyungtae Kang, Jaeyoung Sung, Sunbum Kwon. Metabolism‐inspired chemical reaction networks for chemically driven dissipative oligoesterification. Angewandte Chemie International Edition 2025, 64 (14) https://doi.org/10.1002/anie.202425407
    9. Kevin Qian, Björn Hanf, Christopher Cummins, Dorothea Fiedler. Monodisperse Chemical Oligophosphorylation of Peptides via Protected Oligophosphorimidazolide Reagents. Angewandte Chemie 2025, 137 (11) https://doi.org/10.1002/ange.202419147
    10. Kevin Qian, Björn Hanf, Christopher Cummins, Dorothea Fiedler. Monodisperse Chemical Oligophosphorylation of Peptides via Protected Oligophosphorimidazolide Reagents. Angewandte Chemie International Edition 2025, 64 (11) https://doi.org/10.1002/anie.202419147
    11. Simone M. Poprawa, Michele Stasi, Brigitte A. K. Kriebisch, Monika Wenisch, Judit Sastre, Job Boekhoven. Active droplets through enzyme-free, dynamic phosphorylation. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-48571-z
    12. Antara Reja, Sangam Jha, Ashley Sreejan, Sumit Pal, Subhajit Bal, Chetan Gadgil, Dibyendu Das. Feedback driven autonomous cycles of assembly and disassembly from minimal building blocks. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-54197-y
    13. Peng Zhao, Yuanfeng Zhao, Yan Lu, Linjie Xu, Bohan Li, Yingshuai Zhao, Wei Zhou, Pu Yan, Youfu Wang, Kecheng Cao, Yijun Zheng. Non‐Equilibrium Dissipative Assembly with Switchable Biological Functions. Angewandte Chemie 2024, 136 (48) https://doi.org/10.1002/ange.202409169
    14. Peng Zhao, Yuanfeng Zhao, Yan Lu, Linjie Xu, Bohan Li, Yingshuai Zhao, Wei Zhou, Pu Yan, Youfu Wang, Kecheng Cao, Yijun Zheng. Non‐Equilibrium Dissipative Assembly with Switchable Biological Functions. Angewandte Chemie International Edition 2024, 63 (48) https://doi.org/10.1002/anie.202409169
    15. Sudeep Koppayithodi, Prerna Ranasingh, Nishant Singh. Life in Lab: Chemically Fueled Systems Chemistry for Emergent Properties. ChemSystemsChem 2024, 6 (6) https://doi.org/10.1002/syst.202400028
    16. Mahesh D. Pol, Kun Dai, Ralf Thomann, Sandra Moser, Subhra Kanti Roy, Charalampos G. Pappas. Guiding Transient Peptide Assemblies with Structural Elements Embedded in Abiotic Phosphate Fuels. Angewandte Chemie 2024, 136 (28) https://doi.org/10.1002/ange.202404360
    17. Mahesh D. Pol, Kun Dai, Ralf Thomann, Sandra Moser, Subhra Kanti Roy, Charalampos G. Pappas. Guiding Transient Peptide Assemblies with Structural Elements Embedded in Abiotic Phosphate Fuels. Angewandte Chemie International Edition 2024, 63 (28) https://doi.org/10.1002/anie.202404360
    18. Wade E. Schnorr, W. Seth Childers. Biomolecular Condensates: From Bacterial Compartments to Incubator Spaces of Emergent Chemical Systems in Matter‐to‐Life Transitions. ChemSystemsChem 2024, 6 (4) https://doi.org/10.1002/syst.202400011
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2023, 145, 48, 26086–26094
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.3c07918
    Published November 22, 2023
    Copyright © 2023 American Chemical Society
    Request reuse permissions

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