The identification of a novel SIRT6 modulator from Trigonella foenum-graecum using ligand fishing with protein coated magnetic beads
Autor: | Sebastian D. Fugmann, Kevin Spelman, Nagendra Singh, Ruin Moaddel, Sarangan Ravichandran |
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Rok vydání: | 2014 |
Předmět: |
Naringenin
Trigonella Clinical Biochemistry Vitexin Ligands Biochemistry Article Analytical Chemistry Matrix (chemical analysis) Magnetics chemistry.chemical_compound Escherichia coli Sirtuins Orientin biology Plant Extracts Cell Biology General Medicine biology.organism_classification chemistry Acetylation Seeds Magnets Histone deacetylase Quercetin |
Zdroj: | Journal of Chromatography B. 968:105-111 |
ISSN: | 1570-0232 |
DOI: | 10.1016/j.jchromb.2014.03.016 |
Popis: | SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. Thus the identification of compounds that modulate SIRT6 activity could be of great therapeutic importance. We have previously developed an H3K9 deacetylation guided assay with SIRT6 coated magnetic beads (SIRT6-MB). With the developed assay, we identified quercetin, naringenin and vitexin as SIRT6 inhibitors from T. foenum-graecum seed extract using a candidate approach. Currently, the predominant method for the identification of active compounds from a plant extract is carried out through a dereplication process. A novel targeted approach for the direct identification of active compounds from a complex matrix could save time and resources. Herein, we report the application of the SIRT6-MB for 'fishing' experiments utilizing T. foenum-graecum seed extract. In which orientin, and seventeen other compounds were identified as SIRT6 binders. This is the first use of this method for 'fishing' out active ligands from a botanical matrix, and sets the basis for the identification of active compounds from a complex matrix. |
Databáze: | OpenAIRE |
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