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

Bioorg Med Chem Lett. 2011 Aug 15;21(16):4753-7. doi: 10.1016/j.bmcl.2011.06.069. Epub 2011 Jun 22.

Abstract

In the current study, we have identified N(ε)-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Lysine / analogs & derivatives
  • Lysine / chemistry
  • Lysine / pharmacology*
  • Molecular Structure
  • Sirtuins / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thiocarbamates / chemical synthesis
  • Thiocarbamates / chemistry
  • Thiocarbamates / pharmacology*

Substances

  • Enzyme Inhibitors
  • Thiocarbamates
  • Sirtuins
  • Lysine