New chemical tools for probing activity and inhibition of the NAD+-dependent lysine deacylase sirtuin 2 was written by Swyter, Soeren;Schiedel, Matthias;Monaldi, Daria;Szunyogh, Sandor;Lehotzky, Attila;Rumpf, Tobias;Ova’di, Judit;Sippl, Wolfgang;Jung, Manfred. And the article was included in Philosophical Transactions of the Royal Society, B: Biological Sciences in 2018.Safety of 4-Phenyl-3H,3’H-spiro[furan-2,1′-isobenzofuran]-3,3′-dione This article mentions the following:
Sirtuins are NAD+-dependent protein deacylases capable of cleaving off acetyl as well as other acyl groups from the 1-amino group of lysines in histones and other substrate proteins. They have been reported as promising drug targets, and thus modulators of their activity are needed as mol. tools to uncover their biol. function and as potential therapeutics. Here, we present new assay formats that complement existing assays for sirtuin biochem. and cellular target engagement. Firstly, we report the development of a homogeneous fluorescence-based activity assay using unlabeled acylated peptides. Upon deacylation, the free lysine residue reacts with fluorescamine to form a fluorophore. Secondly, using click chem. with a TAMRA-azide on a propargylated sirtuin inhibitor, we prepared the first fluorescently labeled small-mol. inhibitor of Sirt2. This is used in a binding assay, which is based on fluorescence polarization. We used it successfully to map potential inhibitor-binding sites and also to show cellular Sirt2 engagement. By means of these new assays, we were able to identify and characterize novel Sirt2 inhibitors out of a focused library screen. The binding of the identified Sirt2 inhibitors was rationalized by mol. docking studies. These new chem. tools thus can enhance further sirtuin research. In the experiment, the researchers used many compounds, for example, 4-Phenyl-3H,3’H-spiro[furan-2,1′-isobenzofuran]-3,3′-dione (cas: 38183-12-9Safety of 4-Phenyl-3H,3’H-spiro[furan-2,1′-isobenzofuran]-3,3′-dione).
4-Phenyl-3H,3’H-spiro[furan-2,1′-isobenzofuran]-3,3′-dione (cas: 38183-12-9) belongs to benzofurans derivatives. Benzofurans are compounds with a planar structure having 10 pi electrons that include the lone pair on oxygen atom, which makes it more susceptible to electrophilic attack. Introduction of benzofurans in organic synthesis, particularly drug synthesis, involves generally the use of their metalated species as nucleophiles in addition reactions or in metal-catalysed cross-coupling reactions.Safety of 4-Phenyl-3H,3’H-spiro[furan-2,1′-isobenzofuran]-3,3′-dione
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem