13 転写を制御する小分子有機化合物(口頭発表の部)
スポンサーリンク
概要
- 論文の詳細を見る
Regulation of gene expression by transcription factors touches many aspects of eukaryotic biology, and its systematic, external control by organic molecules represents a challenge in chemistry. Our group has discovered by screening chemical libraries a unique small molecule that modulates gene transcription. The synthetic molecule, named "adamanolol," represents the first small molecule that modulates gene transcription by targeting transcription factor-coactivator interaction. We synthesized adamanolol and its derivatives and obtained structure-activity relationship, which enabled the design of the second-generation compound named "wrenchnolol." Wrenchnolol mimics an alpha-helical activation domain of transcription factor ESX: it may serve as a small-molecule activation module when coupled with a DNA binding molecule. Our group has in fact succeeded in designing a completely organic, synthetic transcription factor that activates transcription in vitro. The results demonstrate that it is possible to generate a transcription factor out of completely organic components. Nevertheless, the first small molecule transcription factor, STF1, had limited cell permeability and was not suited for cell culture or animal studies. We have now synthesized the second generation of small molecule transcription factors with better physical properties. We also developed a series of wrenchnolol analogs that may be more potent in activating transcription. Continued efforts may lead to the design of small-molecule transcription factors whose activities are comparable to those of naturally occurring transcription factors. As another application of wrenchnolol, we synthesized a biotinylated version of wrenchnolol, and examined its ability to activate the muscle cell differentiation in the presence of a fusion protein of streptavidin and the DNA-binding domain of MyoD, a master regulator of myogenesis in human cells. Although the differention rates were not optimized yet, the biotinylated wrenchnolol clearly enhanced the myogenesis in cell culture. The results suggest that wrenchnolol is capable of activating the transcription of endogenous genes once it is recruited to their promoters.
- 天然有機化合物討論会の論文
- 2007-08-24
著者
関連論文
- 49 わらびの究極発癌物質および人工類縁物質による核酸の化学修飾(口頭発表の部)
- 13 転写を制御する小分子有機化合物(口頭発表の部)
- 小分子有機化合物による転写制御 (特集 ケミカルバイオロジーの新たな可能性)
- 合成化合物を起爆剤としたケミカルバイオロジー
- 合成化合物ライブラリーによるケミカルゲノミクスの潮流 (特集 ケミカルゲノミクスの誕生)
- 膜脂質のふしぎ : Pentacycloanammoxic acid の不斉全合成
- P-26 細胞形態変化誘導活性を指標としたアクチン阻害化合物の探索(ポスター発表の部)
- P-77 細胞の接着と増殖を促進するダンベル型小分子化合物アドヘサミンの発見と作用機序(ポスター発表の部)