Identification of the Binding Site of Chroman-4-one-Based Sirtuin 2-Selective Inhibitors using Photoaffinity Labeling in Combination with Tandem Mass Spectrometry

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• 作者：Tina Seifert ; Marcus Malo ; Johan Lengqvist ; Carina Sihlbom ; Elina M. Jarho ; Kristina Luthman
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：December 8, 2016
• 年：2016
• 卷：59
• 期：23
• 页码：10794-10799
• 全文大小：335K
• ISSN：1520-4804

文摘

Photoaffinity labeling (PAL) was used to identify the binding site of chroman-4-one-based SIRT2-selective inhibitors. The photoactive diazirine 4, a potent SIRT2 inhibitor, was subjected to detailed photochemical characterization. In PAL experiments with SIRT2, a tryptic peptide originating from the covalent attachment of photoactivated 4 was identified. The peptide covers both the active site of SIRT2 and the proposed binding site of chroman-4-one-based inhibitors. A high-power LED was used as source for the monochromatic UV light enabling rapid photoactivation.