A mechanism-based potent sirtuin inhibitor containing Nε-thiocarbamoyl-lysine (TuAcK)

In the current study, we have identified Nε-thiocarbamoyl-lysine (TuAcK) as a general sirtuin inhibitory warhead which was shown to be able to confer potent sirtuin inhibition. This inhibition was also shown to be mechanism-based in that the TuAck residue was able to be processed by a sirtuin enzyme with the formation of a stalled S-alkylamidate intermediate.

Nε-Thiocarbamoyl-lysine (TuAcK), an analog of Nε-acetyl-lysine (AcK), was found in the current study to be able to confer potent sirtuin inhibition. This inhibition was also shown to be mechanism-based.Figure optionsDownload as PowerPoint slide