Youngjoo Kwon, Hans-Dieter Arndt, Qian Mao, Yongmun Choi, Yoshinori Kawazoe, Peter B Dervan, Motonari Uesugi
The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Journal of the American Chemical Society 2004 Dec 15Regulation 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. Here we report the design of a completely organic, nonpeptidic compound that mimics a transcription factor. The design takes advantage of the specific DNA-binding affinity of a hairpin polyamide molecule and the ability of wrenchnolol to bind to the Sur-2 subunit of human mediator complex. The hybrid compound of these two molecules activates transcription of a reporter gene in vitro in a promoter-dependent manner through simultaneous contacts with DNA and Sur-2. Our results indicate that it is possible to generate a transcription factor out of nonpeptidic components.
Youngjoo Kwon, Hans-Dieter Arndt, Qian Mao, Yongmun Choi, Yoshinori Kawazoe, Peter B Dervan, Motonari Uesugi. Small molecule transcription factor mimic. Journal of the American Chemical Society. 2004 Dec 15;126(49):15940-1
PMID: 15584709
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