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Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures

Natural products provide an unparalleled diversity of small molecules to fuel drug screening efforts, but deconvoluting the pharmacological activity of natural product mixtures to identify key bioactive compounds remains a vexing and labor-intensive process. Therefore, we have developed a new platfo...

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Detalles Bibliográficos
Autores principales: Seidel, Jeremy, Du, Yongle, Devanathan, Rohin, Law, Richard, Hu, Zhijuan, Zill, Nicholas A., Iavarone, Anthony T., Zhang, Wenjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421080/
https://www.ncbi.nlm.nih.gov/pubmed/37570695
http://dx.doi.org/10.3390/molecules28155726
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author Seidel, Jeremy
Du, Yongle
Devanathan, Rohin
Law, Richard
Hu, Zhijuan
Zill, Nicholas A.
Iavarone, Anthony T.
Zhang, Wenjun
author_facet Seidel, Jeremy
Du, Yongle
Devanathan, Rohin
Law, Richard
Hu, Zhijuan
Zill, Nicholas A.
Iavarone, Anthony T.
Zhang, Wenjun
author_sort Seidel, Jeremy
collection PubMed
description Natural products provide an unparalleled diversity of small molecules to fuel drug screening efforts, but deconvoluting the pharmacological activity of natural product mixtures to identify key bioactive compounds remains a vexing and labor-intensive process. Therefore, we have developed a new platform to probe the non-specific pharmacological potential of compounds present in common dietary supplements via shotgun derivatization with isotopically labeled propanoic acid, a live cell affinity assay, which was used to selectively recognize the population of compounds which bind tightly to HeLa cells in culture, and a computational LC-MS data analysis of isotopically labeled compounds from cell lysate. The data analysis showed that hundreds of compounds were successfully derivatized in each extract, and dozens of those compounds showed high affinity for HeLa cells. In total, over a thousand isotopically labeled compounds were screened for cell affinity across three separate experiments, resulting in the identification of several known bioactive compounds with specific protein targets and six previously unreported structures. The new natural products include three tulsinol compounds which were isolated from Ocimum tenuiflorum and three valeraninium alkaloids from Valeriana officinalis. The valeraninium alkaloids constitute a distinct new family of alkaloids from valerian, which may have previously undescribed bioactivity. These results collectively demonstrate the tag and snag workflow’s viability as a drug discovery method.
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spelling pubmed-104210802023-08-12 Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures Seidel, Jeremy Du, Yongle Devanathan, Rohin Law, Richard Hu, Zhijuan Zill, Nicholas A. Iavarone, Anthony T. Zhang, Wenjun Molecules Article Natural products provide an unparalleled diversity of small molecules to fuel drug screening efforts, but deconvoluting the pharmacological activity of natural product mixtures to identify key bioactive compounds remains a vexing and labor-intensive process. Therefore, we have developed a new platform to probe the non-specific pharmacological potential of compounds present in common dietary supplements via shotgun derivatization with isotopically labeled propanoic acid, a live cell affinity assay, which was used to selectively recognize the population of compounds which bind tightly to HeLa cells in culture, and a computational LC-MS data analysis of isotopically labeled compounds from cell lysate. The data analysis showed that hundreds of compounds were successfully derivatized in each extract, and dozens of those compounds showed high affinity for HeLa cells. In total, over a thousand isotopically labeled compounds were screened for cell affinity across three separate experiments, resulting in the identification of several known bioactive compounds with specific protein targets and six previously unreported structures. The new natural products include three tulsinol compounds which were isolated from Ocimum tenuiflorum and three valeraninium alkaloids from Valeriana officinalis. The valeraninium alkaloids constitute a distinct new family of alkaloids from valerian, which may have previously undescribed bioactivity. These results collectively demonstrate the tag and snag workflow’s viability as a drug discovery method. MDPI 2023-07-28 /pmc/articles/PMC10421080/ /pubmed/37570695 http://dx.doi.org/10.3390/molecules28155726 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Seidel, Jeremy
Du, Yongle
Devanathan, Rohin
Law, Richard
Hu, Zhijuan
Zill, Nicholas A.
Iavarone, Anthony T.
Zhang, Wenjun
Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures
title Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures
title_full Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures
title_fullStr Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures
title_full_unstemmed Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures
title_short Tag and Snag: A New Platform for Bioactive Natural Product Screening from Mixtures
title_sort tag and snag: a new platform for bioactive natural product screening from mixtures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421080/
https://www.ncbi.nlm.nih.gov/pubmed/37570695
http://dx.doi.org/10.3390/molecules28155726
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