The mimics of N ε-acyl-lysine derived from cysteine as sirtuin inhibitors

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2375-2378. doi: 10.1016/j.bmcl.2018.06.030. Epub 2018 Jun 18.


Sirtuin inhibitors as physiological research tools and therapeutic potentials have caught many attentions in last decades. The mimics of acyl lysine have been approved to be a very efficient strategy for development of mechanism-based sirtuin inhibitors. In current study, a novel scaffold of l-S-(3-carboxamidopropyl) cysteine (l-CAPC) has been exploited for design and synthesis of sirtuin inhibitors. As a result, the mimics of Nε-acyl-lysine derived from cysteine including small molecules (5a-m) and peptides (9a-m) have been synthesized. Among these, the peptides 9g and 9h were found to be the most inhibitory potency and selectivity against SIRT2.

Keywords: Mechanism-based inhibitors; SIRT2 inhibitors; Sirtuin inhibitors; The mimics of lysine; l-Cysteine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cysteine / chemistry
  • Cysteine / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Lysine / analogs & derivatives
  • Lysine / chemistry
  • Lysine / pharmacology*
  • Molecular Structure
  • Sirtuins / antagonists & inhibitors*
  • Sirtuins / metabolism
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Sirtuins
  • Lysine
  • Cysteine