title: Synthesis and characterization of a SIRT6 open tubular column: predicting deacetylation activity using frontal chromatography.
abstract: 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.
authors: Biomedical Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
authors: Nagendra
authors: N
authors: Singh
authors: Sarangan
authors: S
authors: Ravichandran
authors: Darrell D
authors: DD
authors: Norton
authors: Sebastian D
authors: SD
authors: Fugmann
authors: Ruin
authors: R
authors: Moaddel
mesh_terms: D047310:Apigenin / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D053801:Capillary Electrochromatography / Q000295:instrumentation* / Q000379:methods; D002846:Chromatography, Affinity / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D044950:Flavanones / Q000378:metabolism / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D044949:Kaempferols / Q000378:metabolism / Q000494:pharmacology; D047311:Luteolin / Q000378:metabolism / Q000494:pharmacology; D008280:Magnetics; D008958:Models, Molecular; D011794:Quercetin / Q000378:metabolism* / Q000494:pharmacology; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D044950:Flavanones; D056572:Histone Deacetylase Inhibitors; D044949:Kaempferols; C006552:kaempferol; D047310:Apigenin; D011794:Quercetin; C032731:vitexin; D037761:Sirtuins; C005273:naringenin; D047311:Luteolin
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