Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone

[Image: see text] Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity...

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Autores principales: Lajkiewicz, Neil J., Cognetta, Armand B., Niphakis, Micah J., Cravatt, Benjamin F., Porco, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978386/
https://www.ncbi.nlm.nih.gov/pubmed/24447064
http://dx.doi.org/10.1021/ja412431g
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author Lajkiewicz, Neil J.
Cognetta, Armand B.
Niphakis, Micah J.
Cravatt, Benjamin F.
Porco, John A.
author_facet Lajkiewicz, Neil J.
Cognetta, Armand B.
Niphakis, Micah J.
Cravatt, Benjamin F.
Porco, John A.
author_sort Lajkiewicz, Neil J.
collection PubMed
description [Image: see text] Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived β-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent β-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells.
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spelling pubmed-39783862015-01-21 Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone Lajkiewicz, Neil J. Cognetta, Armand B. Niphakis, Micah J. Cravatt, Benjamin F. Porco, John A. J Am Chem Soc [Image: see text] Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived β-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent β-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells. American Chemical Society 2014-01-21 2014-02-12 /pmc/articles/PMC3978386/ /pubmed/24447064 http://dx.doi.org/10.1021/ja412431g Text en Copyright © 2014 American Chemical Society
spellingShingle Lajkiewicz, Neil J.
Cognetta, Armand B.
Niphakis, Micah J.
Cravatt, Benjamin F.
Porco, John A.
Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone
title Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone
title_full Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone
title_fullStr Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone
title_full_unstemmed Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone
title_short Remodeling Natural Products: Chemistry and Serine Hydrolase Activity of a Rocaglate-Derived β-Lactone
title_sort remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived β-lactone
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978386/
https://www.ncbi.nlm.nih.gov/pubmed/24447064
http://dx.doi.org/10.1021/ja412431g
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