Total Synthesis and Functional Evaluation of IORs, Sulfonolipidbased Inhibitors of Cell Differentiation in Salpingoeca rosetta

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Druh dokumentu: Článek
ISSN: 1433-7851
1521-3773
DOI: 10.1002/anie.202209105
Popis: 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.
Databáze: Networked Digital Library of Theses & Dissertations
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