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• W3201722867 endingPage "105413" @default.
• W3201722867 startingPage "105413" @default.
• W3201722867 abstract "The mammalian sirtuins are a group of posttranslational modification enzymes that remove acyl modifications from lysine residues in an NAD+-dependent manner. Although initially proposed as histone deacetylases (HDACs), they are now known to target other cellular enzymes and proteins as well. Sirtuin-catalyzed simple amide hydrolysis has profound biological consequences including suppression of gene expression, promotion of DNA damage repair, and regulation of glucose and lipid metabolism. Human sirtuins have been intensively pursued by both academia and industry as potential therapeutic targets for the treatment of diseases such as cancer and neurodegeneration. To gain a better understanding of their roles in various cellular events, innovative chemical probes are highly sought after. This current study focuses on the development of activity-based chemical probes (ABPs) for the profiling of sirtuin activity in biological samples. Cyclooctyne-containing and azido-containing probes were synthesized to enable the subsequent copper-free click conjugation to either a fluorophore or biotin. The two groups of structurally related ABPs demonstrated different labeling efficiency and selectivity: the cyclooctyne-containing probes failed to label recombinant sirtuins to any appreciable level, while the azido-containing ABPs showed good isoform selectivity. The azido-containing ABPs were further analyzed for their ability to label an individual sirtuin isoform in protein mixtures and cell lysates. These biocompatible ABPs allow the study of dynamic cellular protein activity change to become possible." @default.
• W3201722867 created "2021-10-11" @default.
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• W3201722867 date "2021-12-01" @default.
• W3201722867 modified "2023-10-12" @default.
• W3201722867 title "Profiling sirtuin activity using Copper-free click chemistry" @default.
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• W3201722867 doi "https://doi.org/10.1016/j.bioorg.2021.105413" @default.
• W3201722867 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8612980" @default.
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• W3201722867 hasPublicationYear "2021" @default.
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