Histone H3 peptide based LSD1-selective inhibitors

Bioorg Med Chem Lett. 2015 May 1;25(9):1925-8. doi: 10.1016/j.bmcl.2015.03.030. Epub 2015 Mar 20.

Abstract

A series of candidates for the histone H3 peptide based LSD1-selective inhibitor were designed and synthesized. Among peptides 1a-c and 2a-c, peptide 1a, which has a phenylcyclopropylamine (PCPA) moiety at Lys-4 of the 21 amino acid residues of histone H3, was the most potent LSD1-selective inhibitor. Truncation studies of peptide 1a revealed the significance of the peptide sequence length. These findings will be useful for the further development of histone H3 peptide based LSD1-selective inhibitors.

Keywords: Histone H3; Inhibitor; Lysine-specific demethylase 1 (LSD1); Peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Histone Demethylases / antagonists & inhibitors*
  • Histone Demethylases / metabolism
  • Histones / chemistry*
  • Histones / pharmacology
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Histones
  • Histone Demethylases
  • KDM1A protein, human