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

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.
Taeko Kakizawa 1,  Tamio Mizukami 2,  Yukihiro Itoh 3,  Makoto Hasegawa 2,  Ryuzo Sasaki 2,  Takayoshi Suzuki 4
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo 169-8555, Japan.
  • 2 Graduate School of Bio-Science, Nagahama Institute of Bio-Science Technology, 1226 Tamura-cho, Nagahama, Shiga 526-0829, Japan.
  • 3 Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan.
  • 4 Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan. Electronic address: [email protected].
PMID: 26794039 DOI: 10.1016/j.bmcl.2016.01.036
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.

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