Evaluation of phenylcyclopropylamine compounds by enzymatic assay of lysine-specific demethylase 2 in the presence of NPAC peptide

Bioorg Med Chem Lett. 2016 Feb 15;26(4):1193-5. doi: 10.1016/j.bmcl.2016.01.036. Epub 2016 Jan 16.

Abstract

Lysine-specific demethylase 2 (LSD2) demethylates mono- and dimethylated Lys-4 of histone H3 (H3K4me1 and H3K4me2). NPAC protein is known to interact with LSD2 and promote its H3K4 demethylase activity. In this study, we established a demethylation assay system that utilizes recombinant LSD2 in the presence of a synthetic NPAC peptide. Several phenylcyclopropylamine (PCPA)-based inhibitors were examined for their LSD2 inhibitory activity in the LSD2 enzymatic assay with the NPAC peptide. The assay results showed that the PCPA derivatives, including NCD41, selectively inhibited LSD1 in preference to LSD2.

Keywords: Histone H3K4 demethylation; Inhibitor; Lysine-specific demethylases 1 and 2 (LSD1 and LSD2); NPAC peptide.

MeSH terms

  • Amino Acid Sequence
  • Histone Demethylases / antagonists & inhibitors
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Peptides / analysis
  • Peptides / chemistry
  • Peptides / metabolism*
  • Propylamines / chemistry
  • Propylamines / metabolism
  • Protein Binding
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Peptides
  • Propylamines
  • Recombinant Proteins
  • Histone Demethylases
  • KDM1B protein, human
  • KDM1A protein, human