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Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta
The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR‐1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. ros...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825905/ https://www.ncbi.nlm.nih.gov/pubmed/35901418 http://dx.doi.org/10.1002/anie.202209105 |
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author | Raguž, Luka Peng, Chia‐Chi Rutaganira, Florentine U. N. Krüger, Thomas Stanišić, Aleksa Jautzus, Theresa Kries, Hajo Kniemeyer, Olaf Brakhage, Axel A. King, Nicole Beemelmanns, Christine |
author_facet | Raguž, Luka Peng, Chia‐Chi Rutaganira, Florentine U. N. Krüger, Thomas Stanišić, Aleksa Jautzus, Theresa Kries, Hajo Kniemeyer, Olaf Brakhage, Axel A. King, Nicole Beemelmanns, Christine |
author_sort | Raguž, Luka |
collection | PubMed |
description | The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR‐1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta. The synthesis features a decarboxylative cross‐coupling reaction of a sulfonic acid‐containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR‐1A derivatives, including fluorescent and photoaffinity‐based probes, allowed quantification of IOR‐1A, localization studies within S. rosetta cells, and evaluation of structure‐activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta. These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta. |
format | Online Article Text |
id | pubmed-9825905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98259052023-01-09 Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta Raguž, Luka Peng, Chia‐Chi Rutaganira, Florentine U. N. Krüger, Thomas Stanišić, Aleksa Jautzus, Theresa Kries, Hajo Kniemeyer, Olaf Brakhage, Axel A. King, Nicole Beemelmanns, Christine Angew Chem Int Ed Engl Research Articles The choanoflagellate Salpingoeca rosetta is an important model system to study the evolution of multicellularity. In this study we developed a new, modular, and scalable synthesis of sulfonolipid IOR‐1A (six steps, 27 % overall yield), which acts as bacterial inhibitor of rosette formation in S. rosetta. The synthesis features a decarboxylative cross‐coupling reaction of a sulfonic acid‐containing tartaric acid derivative with alkyl zinc reagents. Synthesis of 15 modified IOR‐1A derivatives, including fluorescent and photoaffinity‐based probes, allowed quantification of IOR‐1A, localization studies within S. rosetta cells, and evaluation of structure‐activity relations. In a proof of concept study, an inhibitory bifunctional probe was employed in proteomic profiling studies, which allowed to deduce binding partners in bacteria and S. rosetta. These results showcase the power of synthetic chemistry to decipher the biochemical basis of cell differentiation processes within S. rosetta. John Wiley and Sons Inc. 2022-09-05 2022-10-10 /pmc/articles/PMC9825905/ /pubmed/35901418 http://dx.doi.org/10.1002/anie.202209105 Text en © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Raguž, Luka Peng, Chia‐Chi Rutaganira, Florentine U. N. Krüger, Thomas Stanišić, Aleksa Jautzus, Theresa Kries, Hajo Kniemeyer, Olaf Brakhage, Axel A. King, Nicole Beemelmanns, Christine Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta |
title | Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta
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title_full | Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta
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title_fullStr | Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta
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title_full_unstemmed | Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta
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title_short | Total Synthesis and Functional Evaluation of IORs, Sulfonolipid‐based Inhibitors of Cell Differentiation in Salpingoeca rosetta
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title_sort | total synthesis and functional evaluation of iors, sulfonolipid‐based inhibitors of cell differentiation in salpingoeca rosetta |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825905/ https://www.ncbi.nlm.nih.gov/pubmed/35901418 http://dx.doi.org/10.1002/anie.202209105 |
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