Lysine-specific demethylase 1 (LSD1) is a flavin-dependent enzyme that removes methyl groups from mono- or dimethylated lysine residues at the fourth position of histone H3. We have previously reported several histone H3 peptides containing an LSD1 inactivator motif at Lys-4. In this study, histone H3 peptides having a trans-2-phenylcyclopropylamine (PCPA), a 2,5-dihydro-1H-pyrrole, and a 1,2,3,6-tetrahydropyridine moiety at Lys-4 were prepared along with related compounds possessing a shorter side chain at the fourth position. Enzymatic assays showed that PCPA peptides containing a longer side chain, which can react with FAD in the active site, are potent LSD1-selective inhibitors.

赖氨酸特异性脱甲基酶1（LSD1）是一种黄素依赖性酶，可从组蛋白H3第四位的单或二甲基化赖氨酸残基上除去甲基。我们先前已经报道了几种在Lys-4处含有LSD1失活基序的组蛋白H3肽。在这项研究中，制备了在Lys-4处具有反式-2-苯基环丙胺（PCPA），2,5-二氢-1 H-吡咯和1,2,3,6-四氢吡啶部分的组蛋白H3肽，以及相关化合物在第四个位置具有较短的侧链。酶促测定表明，含有较长侧链的PCPA肽是有效的LSD1选择性抑制剂，可与活性位点中的FAD反应。