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タイトル: | A Multi-target Small Molecule for Targeted Transcriptional Activation of Therapeutically Significant Nervous System Genes |
著者: | Wei, Yulei Pandian, Ganesh N. Zou, Tingting Taniguchi, Junichi Sato, Shinsuke Kashiwazaki, Gengo Vaijayanthi, Thangavel Hidaka, Takuya Bando, Toshikazu Sugiyama, Hiroshi https://orcid.org/0000-0001-8923-5946 (unconfirmed) |
著者名の別形: | 坂東, 俊和 杉山, 弘 |
キーワード: | Brain and nervous system DNA recognition Multi-target small molecules Polymerase chain reaction Synthetic biology |
発行日: | 1-Jan-2016 |
出版者: | Wiley-VCH Verlag |
誌名: | ChemistryOpen |
巻: | 5 |
開始ページ: | 517 |
終了ページ: | 521 |
抄録: | An integrated multi-target small molecule capable of altering dynamic epigenetic and transcription programs associated with the brain and nervous system has versatile applications in the regulation of therapeutic and cell-fate genes. Recently, we have been constructing targeted epigenetic ON switches by integrating sequence-specific DNA binding pyrrole-imidazole polyamides with a potent histone deacetylase inhibitor SAHA. Here, we identified a DNA-based epigenetic ON switch termed SAHA-L as the first-ever multi-target small molecule capable of inducing transcription programs associated with the human neural system and brain synapses networks in BJ human foreskin fibroblasts and 201B7-iPS cells. Ingenuity pathway analysis showed that SAHA-L activates the signaling of synaptic receptors like glutamate and γ-aminobutyric acid, which are key components of autism spectrum disorders. The long-term incubation of SAHA-L in 201B7-iPS cells induced morphology changes and promoted a neural progenitor state. Our finding suggests that the tunable SAHA-L could be advanced as a cell-type-independent multi-target small molecule for therapeutic and/or cell-fate gene modulation. |
著作権等: | © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
URI: | http://hdl.handle.net/2433/218327 |
DOI(出版社版): | 10.1002/open.201600125 |
PubMed ID: | 28032018 |
出現コレクション: | 学術雑誌掲載論文等 |
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