Identification of Covalent Bromodomain Binders through DNA Display of Small Molecules

Article Article scientifique Article Identification of Covalent Bromodomain Binders through DNA Display of Small Molecules eng 2015 author Daguer Jean Pierre 809701 author Zambaldo Claudio 795534 author Abegg Daniel 646062 author Barluenga Badiola Sofia 810177 author Tallant Cynthia author Muller Susanne 41887 author Adibekian Alexander 776158 author Winssinger Nicolas 769664 6057-6061 10.1002/anie.201412276 1433-7851 The regulation of transcriptional programs by epigenetic readers (bromodomains) has been linked to the development of several pathologies. Notably, it has been implicated in the regulation of cellular growth and evasion of apoptosis, in cancer as well as in inflammation. The discovery of small-molecule probes to dissect the role of bromodomains is thus important. We demonstrate that specific cysteine residues conserved across the bromodomains can be harnessed for covalent trapping. We report the discovery of two small molecules that form a covalent bond with cysteine residues conserved across the bromodomain family, analyze the subset of bromodomains that can be addressed through covalent binding, and show proteomic analyses enabled by the enrichment of bromodomains from native lysates. Activity-based proteomic profiling Bromodomains Covalent inhibitors Microarrays Dewey 540 36 Département de chimie organique 141 false Angewandte Chemie 54 20 c307f1af-cb11-4544-a419-afa99d0fe4b5 Article (Published version) Restricted Daguer_et_al-2015-Angewandte_Chemie_International_Edition.pdf 2664728 application/pdf restrictedAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

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Identification of Covalent Bromodomain Binders through DNA Display of Small Molecules	Angewandte Chemie			2015	773	13

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Muller, Susanne