Journal
ANALYTICAL BIOCHEMISTRY
Volume 436, Issue 2, Pages 78-83Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ab.2013.01.018
Keywords
Frontal displacement chromatography; Pharmacophore model; Luteolin; Histone deacetylation assay
Funding
- NIA Intramural Research Program
- National Cancer Institute/National Institutes of Health [HHSN261200800001E]
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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 reported on the identification of quercetin and vitexin as SIRT6 inhibitors, using SIRT6-coated magnetic beads. In this study, we have immobilized SIRT6 onto the surface of an open tubular capillary and characterized the quercetin binding site using frontal displacement chromatography. Structurally related flavonoids were tested for their activity on SIRT6, including apigenin, naringenin, luteolin, and kaempferol. In addition to obtaining their binding activity using frontal affinity chromatographic techniques, we also ranked the compounds based on their ability to displace quercetin. The data suggest that a single displacement curve is representative of the enzymatic activity of the tested ligand. In addition, using the inhibition data obtained in this study, we developed a preliminary pharmacophore model that confirmed the experimental data. Published by Elsevier Inc.
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