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Identification of Covalent Bromodomain Binders through DNA Display of Small Molecules.
Journal article

Identification of Covalent Bromodomain Binders through DNA Display of Small Molecules.

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  • 2015-03-17
Published in:
  • Angewandte Chemie (International ed. in English). - 2015
activity-based proteomic profiling
bromodomains
covalent inhibitors
microarrays
Binding Sites
Cysteine
DNA
Epigenesis, Genetic
Ethacrynic Acid
Humans
Models, Molecular
Molecular Probes
Molecular Structure
Protein Structure, Tertiary
Proteomics
Small Molecule Libraries
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/89687
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