title: Development of programmable small DNA-binding molecules with epigenetic activity for induction of core pluripotency genes.
abstract: Epigenetic modifications that govern the gene expression are often overlooked with the design of artificial genetic switches. N-Methylpyrrole-N-methylimidazole (PI) hairpin polyamides are programmable small DNA binding molecules that have been studied in the context of gene regulation. Recently, we synthesized a library of compounds by conjugating PI polyamides with SAHA, a chromatin-modifier. Among these novel compounds, PI polyamide-SAHA conjugate 1 was shown to epigenetically activate pluripotency genes in mouse embryonic fibroblasts. Here, we report the synthesis of the derivatives of conjugate 1 and demonstrate that these epigenetically active molecules could be developed to improve the induction of pluripotency factors.
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Sakyo, Kyoto 606-8502, Japan.
authors.forename: Ganesh N
authors.initials: GN
authors.lastname: Pandian
authors.forename: Akimichi
authors.initials: A
authors.lastname: Ohtsuki
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sato
authors.forename: Kaori
authors.initials: K
authors.lastname: Hashiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D044127:Epigenesis, Genetic; D006877:Hydroxamic Acids / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D009757:Nylons / Q000737:chemistry*; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D007093:Imidazoles; D009757:Nylons; D000077337:Vorinostat; D004247:DNA; C018100:1-methylimidazole