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Issue 3, 2014
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FP tethering: a screening technique to rapidly identify compounds that disrupt protein–protein interactions

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Abstract

Tethering is a screening technique for discovering small-molecule fragments that bind to pre-determined sites via formation of a disulphide bond. Tethering screens traditionally rely upon mass spectrometry to detect disulphide bond formation, which requires a time-consuming liquid chromatography step. Here we show that tethering can be performed rapidly and inexpensively using a homogenous fluorescence polarization (FP) assay that detects displacement of a peptide ligand from the protein target as an indirect readout of disulphide formation. We apply this method, termed FP tethering, to identify fragments that disrupt the protein–protein interaction between the KIX domain of the transcriptional coactivator CBP and the transcriptional activator peptide pKID.

Graphical abstract: FP tethering: a screening technique to rapidly identify compounds that disrupt protein–protein interactions

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Publication details

The article was received on 26 Nov 2013, accepted on 23 Dec 2013 and first published on 09 Jan 2014


Article type: Concise Article
DOI: 10.1039/C3MD00356F
Citation: Med. Chem. Commun., 2014,5, 370-375
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    FP tethering: a screening technique to rapidly identify compounds that disrupt protein–protein interactions

    J. M. Lodge, T. Justin Rettenmaier, J. A. Wells, W. C. Pomerantz and A. K. Mapp, Med. Chem. Commun., 2014, 5, 370
    DOI: 10.1039/C3MD00356F

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