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Updated: Jul 19, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
A wrench-shaped synthetic molecule that modulates a transcription factor-coactivator interaction
Hiroki Shimogawa1, Youngjoo Kwon, Qian Mao
1The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Development of synthetic molecules that provide external control over the transcription of a given gene represents a challenge in medicinal and bioorganic chemistry. Here we report design and analysis of wrenchnolol, a wrench-shaped synthetic molecule that impairs the transcription of the Her2 oncogene by disrupting association of transcription factor ESX with its coactivator Sur-2. The "jaw" part of the compound mimics the alpha-helical interface of the activation domain of ESX, and the "handle" region accepts chemical modifications for a range of analysis. A water-soluble handle permitted NMR study in aqueous solution; a biotinylated handle verified the selectivity of the interaction, and a fluorescent handle confirmed the cell permeability of the compound. The case study of wrenchnolol foreshadows the promise and the challenge of targeting protein-protein interactions in the nucleus and may lead to the development of unique synthetic modulators of gene transcription.
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