The identification of novel modulators for the SIRT‐6 protein

Abstract

ObjectiveSIRT6 has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age‐associated diseases. The aim of this study was to develop a screening method for the identification of novel modulators of SIRT6 from a natural plant extract.MethodsSIRT6 was immobilized onto the surface of magnetic beads (SIRT6‐MB), and the enzymatic activity was measured. Subsequently, SIRT6 was immobilized onto the surface of an open tubular capillary and characterized by frontal chromatography.ResultsThe identification of quercetin, vitexin as inhibitors from Trigonella foenum‐graecum was carried out. Structurally related flavonoids were then tested for their activity on SIRT6. In addition to obtaining their binding activity, they were also ranked based on their ability to displace quercetin. Further, preliminary results with ligand fishing experiments using the SIRT6‐MB suggest the identification of additional compounds from fenugreek seed extract with activity at the SIRT6‐protein.ConclusionThe SIRT6‐MBs were successfully used for the identification of an active ligand from a botanical matrix, which sets the basis for identification of SIRT6 modulators from plant extracts.