Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F24%3A00081376" target="_blank" >RIV/00159816:_____/24:00081376 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60076658:12520/24:43908122 RIV/00216224:14310/24:00136810

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/abs/pii/S0304389424008197?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S0304389424008197?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jhazmat.2024.134240" target="_blank" >10.1016/j.jhazmat.2024.134240</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry

Popis výsledku v původním jazyce

Surface and treated wastewater are contaminated with highly complex mixtures of micropollutants, which may cause numerous adverse effects, often mediated by endocrine disruption. However, there is limited knowledge regarding some important modes of action, such as interference with thyroid hormone (TH) regulation, and the compounds driving these effects. This study describes an effective approach for the identification of compounds with the potential to bind to transthyretin (TTR; protein distributing TH to target tissues), based on their specific separation in a pull -down assay followed by non -target analysis (NTA). The method was optimized with known TTR ligands and applied to complex water samples. The specific separation of TTR ligands provided a substantial reduction of chromatographic features from the original samples. The applied NTA workflow resulted in the identification of 34 structures. Twelve compounds with available standards were quantified in the original extracts and their TH-displacement potency was confirmed. Eleven compounds were discovered as TTR binders for the first time and linear alkylbenzene sulfonates (LAS) were highlighted as contaminants of concern. Pull -down assay combined with NTA proved to be a well -functioning approach for the identification of unknown bioactive compounds in complex mixtures with great application potential across various biological targets and environmental compartments.

Název v anglickém jazyce

Identification of new endocrine disruptive transthyretin ligands in polluted waters using pull-down assay coupled to non-target mass spectrometry

Popis výsledku anglicky

Surface and treated wastewater are contaminated with highly complex mixtures of micropollutants, which may cause numerous adverse effects, often mediated by endocrine disruption. However, there is limited knowledge regarding some important modes of action, such as interference with thyroid hormone (TH) regulation, and the compounds driving these effects. This study describes an effective approach for the identification of compounds with the potential to bind to transthyretin (TTR; protein distributing TH to target tissues), based on their specific separation in a pull -down assay followed by non -target analysis (NTA). The method was optimized with known TTR ligands and applied to complex water samples. The specific separation of TTR ligands provided a substantial reduction of chromatographic features from the original samples. The applied NTA workflow resulted in the identification of 34 structures. Twelve compounds with available standards were quantified in the original extracts and their TH-displacement potency was confirmed. Eleven compounds were discovered as TTR binders for the first time and linear alkylbenzene sulfonates (LAS) were highlighted as contaminants of concern. Pull -down assay combined with NTA proved to be a well -functioning approach for the identification of unknown bioactive compounds in complex mixtures with great application potential across various biological targets and environmental compartments.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

20700 - Environmental engineering

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JOURNAL OF HAZARDOUS MATERIALS

ISSN

0304-3894

e-ISSN

1873-3336

Svazek periodika

471

Číslo periodika v rámci svazku

JUN

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

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Kód UT WoS článku

001237342400001

EID výsledku v databázi Scopus

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