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|Title:||Molecular rotors as conditionally fluorescent labels for rapid detection of biomolecular interactions|
|Citation:||Goh, W.L., Lee, M.Y., Joseph, T.L., Quah, S.T., Brown, C.J., Verma, C., Brenner, S., Ghadessy, F.J., Teo, Y.N. (2014-04-30). Molecular rotors as conditionally fluorescent labels for rapid detection of biomolecular interactions. Journal of the American Chemical Society 136 (17) : 6159-6162. ScholarBank@NUS Repository. https://doi.org/10.1021/ja413031h|
|Abstract:||We demonstrate the use of fluorescent molecular rotors as probes for detecting biomolecular interactions, specifically peptide-protein interactions. Molecular rotors undergo twisted intramolecular charge transfer upon irradiation, relax via the nonradiative torsional relaxation pathway, and have been typically used as viscosity probes. Their utility as a tool for detecting specific biomolecular interactions has not been explored. Using the well characterized p53-Mdm2 interaction as a model system, we designed a 9-(2-carboxy-2-cyanovinyl) julolidine-based p53 peptide reporter, JP1-R, which fluoresces conditionally only upon Mdm2 binding. The reporter was used in a rapid, homogeneous assay to screen a fragment library for antagonists of the p53-Mdm2 interaction, and several inhibitors were identified. Subsequent validation of these hits using established secondary assays suggests increased sensitivity afforded by JP1-R. The fluorescence of molecular rotors contingent upon target binding makes them a versatile tool for detecting specific biomolecular interactions. © 2014 American Chemical Society.|
|Source Title:||Journal of the American Chemical Society|
|Appears in Collections:||Staff Publications|
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