title: Histone H3 peptide based LSD1-selective inhibitors.
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.
authors.affiliation: Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo 169-8555, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Kakizawa
authors.affiliation: Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ota
authors.affiliation: Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tsumoto
authors.affiliation: Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 1-5 Shimogamohangi-cho, Sakyo-ku, Kyoto 606-0823, Japan; CREST, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: suzukit@koto.kpu-m.ac.jp.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Histone H3; Inhibitor; Lysine-specific demethylase 1 (LSD1); Peptide