Design and characterization of an active site selective caspase-3 transnitrosating agent

ACS Chem Biol. 2006 Nov 21;1(10):659-65. doi: 10.1021/cb600393x.


The oxidative addition of nitric oxide (NO) to a thiol, S-nitrosation, is a focus of studies on cyclic guanosine monophosphate (cGMP)-independent NO signaling. S-Nitrosation of the catalytic cysteine of the caspase proteases has important effects on apoptosis and consequently has received attention. Here we report on a small molecule that can directly probe the effects of S-nitrosation on the caspase cascade. This chemical tool is capable of permeating the mammalian cell membrane, selectively transnitrosating the caspase-3 active site cysteine, and halting apoptosis in cultured human T-cells. The efficacy of this reagent was compared with the commonly used reagent S-nitrosoglutathione and an esterified derivative.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Binding Sites
  • Biotin / chemistry
  • Caspase 3 / chemistry*
  • Caspase 9 / metabolism
  • Chemistry, Pharmaceutical / methods*
  • Cyclic GMP / metabolism
  • Cysteine / chemistry
  • Drug Design
  • Enzyme Activation
  • Humans
  • Kinetics
  • Nitric Oxide / chemistry*
  • Nitric Oxide / metabolism
  • Nitrosation*
  • Peptides / chemistry


  • Peptides
  • Nitric Oxide
  • Biotin
  • Caspase 3
  • Caspase 9
  • Cyclic GMP
  • Cysteine