N(epsilon)-thioacetyl-lysine-containing tri-, tetra-, and pentapeptides as SIRT1 and SIRT2 inhibitors

J Med Chem. 2009 Apr 9;52(7):2153-6. doi: 10.1021/jm801401k.

Abstract

N()-Thioacetyl-lysine-containing tri-, tetra-, and pentapeptides, based on the alpha-tubulin and p53 protein sequences, were studied as SIRT1 and SIRT2 inhibitors. The potency of the pentapeptides depended on the selection of the side chains. The removal of N- and C-terminal residues of the pentapeptides yielded tripeptides with retained SIRT1 inhibitory activity but decreased SIRT2 inhibitory activity. The most potent SIRT1 inhibitors were equipotent with the reference compound (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) with the IC(50) values of 180-330 nM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Lysine / analogs & derivatives*
  • Lysine / chemical synthesis
  • Lysine / chemistry
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuins / antagonists & inhibitors*
  • Sirtuins / chemistry
  • Structure-Activity Relationship
  • Tubulin / chemistry
  • Tumor Suppressor Protein p53 / chemistry

Substances

  • N(epsilon)-thioacetyllysine
  • Oligopeptides
  • Tubulin
  • Tumor Suppressor Protein p53
  • SIRT1 protein, human
  • SIRT2 protein, human
  • Sirtuin 1
  • Sirtuin 2
  • Sirtuins
  • Lysine