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Sirtuins are unique posttranslational modification enzymes that utilize NAD+ as the co-substrate to remove acyl groups from lysine residues. The deacylation events result in profound biological consequences, from transcription silencing to metabolism regulation. This article focuses on a newly developed technology using activity-based chemical probes to report sirtuin functional state in various settings. These chemical probes, thioacyllysine peptides carrying photo-cross-linker as well as bioorthogonal functionality, target the ac

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