312504-53-3Relevant articles and documents
Wrenchnolol derivative optimized for gene activation in cells
Jung, Dongju,Shimogawa, Hiroki,Kwon, Youngjoo,Mao, Qian,Sato, Shin-ichi,et al.
supporting information; experimental part, p. 4774 - 4782 (2009/09/26)
Naturally occurring transcription factors usually have two independent domains, a DNA-binding domain and an activation domain. In designing a synthetic small molecule that mimics a transcription factor, each of the two domains needs to be replaced by small-molecule counterparts. Results of the present study show that derivatives of wrenchnolol, a synthetic molecule that interacts with Sur-2 coactivator, serve as activation modules and stimulate gene transcription in vitro and in cells when tethered to a DNA-binding molecule. Thirteen derivatives of wrenchnolol were chemically synthesized and tested for their ability to activate transcription in vitro and in cells. When tethered to the GAL4 DNA-binding domain, one derivative increased transcription of a GAL4-responsive reporter genein cells 9-fold. This optimized derivative also induced up to 45percent myogenesis of C2C12 cells when tethered to the DNA-binding domain of my ogenic transcription factor MyoD. This optimized derivative may serve asa starting point for designing biological tools or components of fully synthetic transcription factors that permit selective up-regulation of g enes.
