674774-74-4Relevant articles and documents
SMALL MOLECULE INHIBITORS OF HER2 EXPRESSION
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Page/Page column Sheet 29, (2008/06/13)
Peptide mimetic small molecule inhibitors of Sur-2 are provided having the general formula (I).
A Wrench-Shaped Synthetic Molecule that Modulates a Transcription Factor-Coactivator Interaction
Shimogawa, Hiroki,Kwon, Youngjoo,Mao, Qian,Kawazoe, Yoshinori,Choi, Yongmun,Asada, Shinichi,Kigoshi, Hideo,Uesugi, Motonari
, p. 3461 - 3471 (2007/10/03)
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 α-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.