Acetylation of the Catalytic Lysine Inhibits Kinase Activity in PI3K未 was written by Fournier, Julie C. L.;Evans, John P.;Zappacosta, Francesca;Thomas, Daniel A.;Patel, Vipulkumar K.;White, Gemma V.;Campos, Sebastien;Tomkinson, Nicholas C. O.. And the article was included in ACS Chemical Biology in 2021.Quality Control of Tetrahydropyran-4-yl-carboxylic acid This article mentions the following:
Covalent inhibition is a powerful strategy to develop potent and selective small mol. kinase inhibitors. Targeting the conserved catalytic lysine is an attractive method for selective kinase inactivation. The authors have developed novel, selective inhibitors of phosphoinositide 3-kinase 未 (PI3K未) which acylate the catalytic lysine, Lys779, using activated esters as the reactive electrophiles. The acylating agents were prepared by adding the activated ester motif to a known selective dihydroisobenzofuran PI3K未 inhibitor. Three esters were designed, including an acetate ester which was the smallest lysine modification evaluated. Covalent binding to the enzyme was characterized by intact protein mass spectrometry of the PI3K未-ester adducts. An enzymic digest coupled with tandem mass spectrometry identified Lys779 as the covalent binding site, and a biochem. activity assay confirmed that PI3K未 inhibition was a direct result of covalent lysine acylation. A simple chem. modification such as lysine acetylation is sufficient to inhibit kinase activity. The selectivity of the compounds was evaluated against lipid kinases in cell lysates using a chemoproteomic binding assay. Due to the conserved nature of the catalytic lysine across the kinome, the authors believe the covalent inhibition strategy presented here could be applicable to a broad range of clin. relevant targets. In the experiment, the researchers used many compounds, for example, Tetrahydropyran-4-yl-carboxylic acid (cas: 5337-03-1Quality Control of Tetrahydropyran-4-yl-carboxylic acid).
Tetrahydropyran-4-yl-carboxylic acid (cas: 5337-03-1) belongs to tetrahydropyran derivatives. Dihydropyrans and tetrahydropyrans are examples of cyclic ethers widespread in nature. The Prins reaction of homoallylic alcohols with aldehydes afforded an alternative method for the preparation of tetrahydropyrans.Quality Control of Tetrahydropyran-4-yl-carboxylic acid
Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics