The identification of a novel SIRT6 modulator from Trigonella foenum-graecum using ligand fishing with protein coated magnetic beads.
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.
Biomedical Research Center, National institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA.
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N
Singh
Advanced Biomedical Computing Center, Information Systems Program, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, MD 21702, USA.
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Ravichandran
Health, Education & Research in Botanical Medicine, 2209 Dollarhide Way, Ashland, OR 97520, USA.
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Spelman
Department of Biomedical Sciences, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Taiwan.
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Fugmann
Biomedical Research Center, National institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Suite 100, Baltimore, MD 21224, USA. Electronic address: moaddelru@grc.nia.nih.gov.
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Moaddel
D004926:Escherichia coli / Q000378:metabolism; D008024:Ligands; D008280:Magnetics / Q000379:methods*; D059346:Magnets / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D037761:Sirtuins / Q000378:metabolism*; D029910:Trigonella / Q000737:chemistry*
D008024:Ligands; D010936:Plant Extracts; D037761:Sirtuins
Fenugreek seed extract; Ligand fishing; Magnetic beads; Orientin; SIRT6