Small molecule transcription factor mimic
Abstract
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. 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.
Additional Information
© 2004 American Chemical Society. Received September 10, 2004; Publication Date (Web): November 19, 2004. We thank H. Shimogawa and H. Kigoshi for supplying synthetic intermediates, Y. Kang for a plasmid construct, and J. H. Wilson for critical review of the manuscript. Supported by NIH Grants GM071800-01 (M.U.) and GM51747 (P.B.D.), Welch Foundation Grant Q-1490 (M.U.), and U.S. Army Grant DAMD17-02-1-0277 (Y.C.). Supported by DAAD postdoctoral fellowship (H.D.A.).Attached Files
Supplemental Material - ja0445140si20040910_103610.pdf
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Additional details
- Eprint ID
- 66766
- Resolver ID
- CaltechAUTHORS:20160509-114908919
- NIH
- GM071800-01
- NIH
- GM-51747
- Welch Foundation
- Q-1490
- U.S. Army
- DAMD17-02-1-0277
- Deutscher Akademischer Austauschdienst (DAAD)
- Created
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2016-05-17Created from EPrint's datestamp field
- Updated
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2021-11-11Created from EPrint's last_modified field