FP tethering: A screening technique to rapidly identify compounds that disrupt protein-protein interactions

Jean M. Lodge, T. Justin Rettenmaier, James A. Wells, William C. Pomerantz, Anna K. Mapp

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)370-375
Number of pages6
JournalMedChemComm
Volume5
Issue number3
DOIs
StatePublished - Mar 2014

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